Author Report for: Yang ZNo contact information in database for Yang Z
Chen YH, Tian W, Yasuda M, Ye Z, Song M, Mandel U, Kristensen C, Povolo L, Marques ARA and Clausen H <8 more author(s)> Chen YH, Tian W, Yasuda M, Ye Z, Song M, Mandel U, Kristensen C, Povolo L, Marques ARA, Caval T, Heck AJR, Sampaio JL, Johannes L, Tsukimura T, Desnick R, Vakhrushev SY, Yang Z, Clausen H (- 8) Ref: Front Bioeng Biotechnol, 11:1128371, 2023 : PubMed ESTHER: Chen_2023_Front.Bioeng.Biotechnol_11_1128371 PubMedSearch: Chen 2023 Front.Bioeng.Biotechnol 11 1128371 PubMedID: 36911201 Abstract Currently available enzyme replacement therapies for lysosomal storage diseases are limited in their effectiveness due in part to short circulation times and suboptimal biodistribution of the therapeutic enzymes. We previously engineered Chinese hamster ovary (CHO) cells to produce alpha-galactosidase A (GLA) with various N-glycan structures and demonstrated that elimination of mannose-6-phosphate (M6P) and conversion to homogeneous sialylated N-glycans prolonged circulation time and improved biodistribution of the enzyme following a single-dose infusion into Fabry mice. Here, we confirmed these findings using repeated infusions of the glycoengineered GLA into Fabry mice and further tested whether this glycoengineering approach, Long-Acting-GlycoDesign (LAGD), could be implemented on other lysosomal enzymes. LAGD-engineered CHO cells stably expressing a panel of lysosomal enzymes [aspartylglucosamine (AGA), beta-glucuronidase (GUSB), cathepsin D (CTSD), tripeptidyl peptidase (TPP1), alpha-glucosidase (GAA) or iduronate 2-sulfatase (IDS)] successfully converted all M6P-containing N-glycans to complex sialylated N-glycans. The resulting homogenous glycodesigns enabled glycoprotein profiling by native mass spectrometry. Notably, LAGD extended the plasma half-life of all three enzymes tested (GLA, GUSB, AGA) in wildtype mice. LAGD may be widely applicable to lysosomal replacement enzymes to improve their circulatory stability and therapeutic efficacy. Title: Two birds with one stone: An enzyme-regulated ratiometric fluorescent and photothermal dual-mode probe for organophosphorus pesticide detection Jiang W, Yang Z, Tong F, Zhang S, Zhu L, Wang L, Huang L, Liu K, Zheng M and Liu Y <2 more author(s)> Jiang W, Yang Z, Tong F, Zhang S, Zhu L, Wang L, Huang L, Liu K, Zheng M, Zhou Y, Hou R, Liu Y (- 2) Ref: Biosensors & Bioelectronics, 224:115074, 2023 : PubMed ESTHER: Jiang_2023_Biosens.Bioelectron_224_115074 PubMedSearch: Jiang 2023 Biosens.Bioelectron 224 115074 PubMedID: 36638562 Abstract In this study, based on the oxidase activity and photothermal effect of manganese dioxide nanosheets (MnO(2) NSs), with thiamine (TH) as the fluorescence response signal and tris (2,2'-bipyridyl) ruthenium (II) hexahydrate as the reference signal, an enzyme-regulated ratiometric fluorescence and photothermal dual-mode probe was constructed for the quantitative detection of organophosphorus pesticide (OPs) residues. OPs reduced the production of the reductive product thiocholine by inhibiting the activity of acetylcholinesterase, thereby regulating the residual amount of MnO(2) NSs. With the increase of OPs concentration, the color of the probe solution gradually transitioned from red to blue, and the temperature gradually increased. Using dichlorvos and chlorpyrifos as pesticide models, the developed probes exhibited sensitive responses to OPs in a wide linear range of 0.1-8000sng/mL. The detection limits of dichlorvos and chlorpyrifos in fluorescence mode were 1.13sxs10(-3)sng/mL and 0.86sng/mL, respectively. The corresponding detection limits in photothermal mode were 1.01sng/mL and 1.02sng/mL, respectively. The proposed probe displayed excellent anti-interference and reliability in the analysis of OPs residues in real samples. The dual-mode probe with self-verification function is expected to provide more accurate and robust detection results than the single-mode probe, and has a wider application prospect. Title: Endocannabinoids regulate cocaine-associated memory through brain AEA-CB1R signalling activation Li H, Chen R, Zhou Y, Wang H, Sun L, Yang Z, Bai L, Zhang J Ref: Mol Metab, :101597, 2022 : PubMed ESTHER: Li_2022_Mol.Metab__101597 PubMedSearch: Li 2022 Mol.Metab 101597 PubMedID: 36096452 Abstract OBJECTIVE: Contextual drug-associated memory precipitates craving and relapse in substance users, and the risk of relapse is a major challenge in the treatment of substance use disorders. Thus, understanding the neurobiological underpinnings of how this association memory is formed and maintained will inform future advances in the treatment of drug addiction. Brain endocannabinoids (eCBs) signalling has been associated with drug-induced neuroadaptations, but the role of lipases that mediate small lipid ligand biosynthesis and metabolism in regulating drug-associated memory has not been examined. Here, we explored how manipulation of the lipase fatty acid amide hydrolase (FAAH), which is involved in mediating the level of the lipid ligand anandamide (AEA), affects cocaine-associated memory formation. METHODS: We applied behavioural, pharmacological and biochemical methods to detect cocaine-associated memory formation, eCBs in the dorsal dentate gyrus (dDG), and the activity of related enzymes. We further examined the roles of abnormal FAAH activity and AEA-CB1R signalling in the regulation of cocaine-associated memory formation and granule neuron dendritic structure alterations in the dDG through Western blotting, electron microscopy and immunofluorescence. RESULTS: In the present study, we found that cocaine induced a decrease in the level of FAAH in the dDG and increased the level of AEA. A high level of AEA activated cannabinoid type 1 receptors (CB1Rs) and further triggered CB1R signalling activation and granule neuron dendritic remodelling, and these effects were reversed by blockade of CB1Rs in the brain. Furthermore, inhibition of FAAH in the dDG markedly increased AEA levels and promoted cocaine-associated memory formation through CB1R signalling activation. CONCLUSIONS: Together, our findings demonstrate that the lipase FAAH influences CB1R signalling activation and granule neuron dendritic structure alteration in the dDG by regulating AEA levels and that AEA and AEA metabolism play a key role in cocaine-associated memory formation. Manipulation of AEA production may serve as a potential therapeutic strategy for drug addiction and relapse prevention. Title: Synthesis, Characterization and Biological Evaluation of Benzothiazole-Isoquinoline Derivative Liu C, Guan S, E J, Yang Z, Zhang X, Ju J, Wang S, Zhang H, Liu W and Guan L <6 more author(s)> Liu C, Guan S, E J, Yang Z, Zhang X, Ju J, Wang S, Zhang H, Liu W, Zhao D, He Z, Hu Y, Zhu Y, Zhang L, Jin L, Guan L (- 6) Ref: Molecules, 27:, 2022 : PubMed ESTHER: Liu_2022_Molecules_27_ PubMedSearch: Liu 2022 Molecules 27 PubMedID: 36364337 36558194 Abstract Currently, no suitable clinical drugs are available for patients with neurodegenerative diseases complicated by depression. Based on a fusion technique to create effective multi-target-directed ligands (MTDLs), we synthesized a series of (R)-N-(benzo[d]thiazol-2-yl)-2-(1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl) acetamides with substituted benzothiazoles and (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline. All compounds were tested for their inhibitory potency against monoamine oxidase (MAO) and cholinesterase (ChE) by in vitro enzyme activity assays, and further tested for their specific inhibitory potency against monoamine oxidase B (MAO-B) and butyrylcholinesterase (BuChE). Among them, six compounds (4b-4d, 4f, 4g and 4i) displayed excellent activity. The classical antidepressant forced swim test (FST) was used to verify the in vitro results, revealing that six compounds reduced the immobility time significantly, especially compound 4g. The cytotoxicity of the compounds was assessed by the MTT method and Acridine Orange (AO) staining, with cell viability found to be above 90% at effective compound concentrations, and not toxic to L929 cells reversibility, kinetics and molecular docking studies were also performed using compound 4g, which showed the highest MAO-B and BuChE inhibitory activities. The results of these studies showed that compound 4g binds to the primary interaction sites of both enzymes and has good blood-brain barrier (BBB) penetration. This study provides new strategies for future research on neurodegenerative diseases complicated by depression. Title: Marine fungal metabolite butyrolactone I prevents cognitive deficits by relieving inflammation and intestinal microbiota imbalance on aluminum trichloride-injured zebrafish Nie Y, Yang J, Zhou L, Yang Z, Liang J, Liu Y, Ma X, Qian Z, Hong P and Zhang Y <2 more author(s)> Nie Y, Yang J, Zhou L, Yang Z, Liang J, Liu Y, Ma X, Qian Z, Hong P, Kalueff AV, Song C, Zhang Y (- 2) Ref: J Neuroinflammation, 19:39, 2022 : PubMed ESTHER: Nie_2022_J.Neuroinflammation_19_39 PubMedSearch: Nie 2022 J.Neuroinflammation 19 39 PubMedID: 35130930 Abstract BACKGROUND: Mounting evidences indicate that oxidative stress, neuroinflammation, and dysregulation of gut microbiota are related to neurodegenerative disorders (NDs). Butyrolactone I (BTL-I), a marine fungal metabolite, was previously reported as an in vitro neuroprotectant and inflammation inhibitor. However, little is known regarding its in vivo effects, whereas zebrafish (Danio rerio) could be used as a convenient in vivo model of toxicology and central nervous system (CNS) diseases. METHODS: Here, we employed in vivo and in silico methods to investigate the anti-NDs potential of BTL-I. Specifically, we established a cognitive deficit model in zebrafish by intraperitoneal (i.p.) injection of aluminum trichloride (AlCl(3)) (21 microg) and assessed their behaviors in the T-maze test. The proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) as well as acetylcholinesterase (AChE) activity or glutathione (GSH) levels were assayed 24 h after AlCl(3) injection. The intestinal flora variation of the zebrafish was investigated by 16S rDNA high-throughput analysis. The marine fungal metabolite, butyrolactone I (BTL-I), was used to modulate zebrafish cognitive deficits evoked by AlCl(3) and evaluated about its effects on the above inflammatory, cholinergic, oxidative stress, and gut floral indicators. Furthermore, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug-likeness properties of BTL-I were studied by the in silico tool ADMETlab. RESULTS: BTL-I dose-dependently ameliorated AlCl(3)-induced cognitive deficits in zebrafish. While AlCl(3) treatment elevated the levels of central and peripheral proinflammatory cytokines, increased AChE activity, and lowered GSH in the brains of zebrafish, these effects, except GSH reduction, were reversed by 25-100 mg/kg BTL-I administration. Besides, 16S rDNA high-throughput sequencing of the intestinal flora of zebrafish showed that AlCl(3) decreased Gram-positive bacteria and increased proinflammatory Gram-negative bacteria, while BTL-I contributed to maintaining the predominance of beneficial Gram-positive bacteria. Moreover, the in silico analysis indicated that BTL-I exhibits acceptable drug-likeness and ADMET profiles. CONCLUSIONS: The present findings suggest that BTL-I is a potential therapeutic agent for preventing CNS deficits caused by inflammation, neurotoxicity, and gut flora imbalance. Title: Chlorophyll Inhibits the Digestion of Soybean Oil in Simulated Human Gastrointestinal System Wang X, Li Y, Shen S, Yang Z, Zhang H, Zhang Y Ref: Nutrients, 14:, 2022 : PubMed ESTHER: Wang_2022_Nutrients_14_ PubMedSearch: Wang 2022 Nutrients 14 PubMedID: 35565719 Abstract Nowadays, much available processed and highly palatable food such as cream products and fried and convenient food, which usually showed a high energy density, had caused an increase in the intake of dietary lipids, further leading to significant growth in the prevalence of obesity. Chlorophyll, widespread in fruits and vegetables, was proven to have beneficial effects on alleviating obesity. This study investigated the effects of chlorophyll on the digestive characteristics of lipids under in vitro simulated adult and infant gastrointestinal systems. Chlorophyll decreased the release rate of free fatty acid (FFA) during in vitro adult and infant intestinal digestion by 69.2% and 60.0%, respectively. Meanwhile, after gastrointestinal digestion, chlorophyll changed the FFA composition of soybean oil emulsion and increased the particle size of oil droplets. Interestingly, with the addition of chlorophyll, the activity of pancreatic lipase was inhibited during digestion, which may be related to pheophytin (a derivative of chlorophyll after gastric digestion). Therefore, the results obtained from isothermal titration calorimetry and molecular docking further elucidated that pheophytin could bind to pancreatic lipase with a strong affinity of (4.38 +/- 0.76) x 10(7) M(-1) (K(a)), while the binding site was amino acid residue Trp253. The investigation not only explained why chlorophyll inhibited digestive enzyme activity to reduce lipids digestion but also provided exciting opportunities for developing novel chlorophyll-based healthy products for dietary application in preventing obesity. Title: Progress in enrichment of n-3 polyunsaturated fatty acid: a review Xie D, Chen Y, Yu J, Yang Z, Wang X Ref: Crit Rev Food Sci Nutr, :1, 2022 : PubMed ESTHER: Xie_2022_Crit.Rev.Food.Sci.Nutr__1 PubMedSearch: Xie 2022 Crit.Rev.Food.Sci.Nutr 1 PubMedID: 35699651 Abstract n-3 Polyunsaturated fatty acids (n-3 PUFA) has been widely used in foods, and pharmaceutical products due to its beneficial effects. The content of n-3 PUFA in natural oils is usually low, which decreases its added value. Thus, there is an increasing demand on the market for n-3 PUFA concentrates. This review firstly introduces the differences in bioavailability and oxidative stability between different types of PUFA concentrate (free fatty acid, ethyl ester and acylglycerol), and then provides a comprehensive discussion of different methods for enrichment of lipids with n-3 PUFA including physical-chemical methods and enzymatic methods. Lipases used for catalyzing esterification, transesterification and hydrolysis reactions play an important role in the production of highly enriched various types of n-3 PUFA concentrates. Lipase-catalyzed alcoholysis or hydrolysis reactions are the mostly employed method to prepare high-quality n-3 PUFA of structural acylglycerols. Although many important advantages offered by lipases in enrichment of n-3 PUFA, the high cost of enzyme limits its industrial-scale production. Further research should focus on looking for biological enzymes with extraordinary catalytic ability and clear selectivity. Other novel technologies such as protein engineering and immobilization may be needed to modify lipases to improve its selectivity, catalytic ability and reuse. Title: Effects of urea application on the reproduction of Pardosa pseudoannulata: Field and laboratory studies Yang Z, Wang Y, Wang K, Zhang Y, Yu N, Liu Z Ref: Chemosphere, 301:134697, 2022 : PubMed ESTHER: Yang_2022_Chemosphere_301_134697 PubMedSearch: Yang 2022 Chemosphere 301 134697 PubMedID: 35513078 Abstract As an important chemical fertilizer, urea can greatly increase crop yields, but it also has negative effects on beneficial arthropods in the agricultural field, such as spiders. Here, we reported that urea application reduced the reproductive performance in Pardosa pseudoannulata, a dominant species of spider in rice fields, which preys on a range of insect pests, based on both field and laboratory studies. In a field test, urea application significantly reduced the egg production of adult and subadult females collected from the urea-treated fields. A laboratory test was set up to further evaluate the impact of urea application on P. pseudoannulata reproduction. In consistent with field test results, the spiders treated by urea for 14 d and 28 d had lower reproduction ability than their control counterparts, with regard to the mating rate, egg production, and egg hatchability. The transcriptomic sequencing of individuals treated by urea for 28 d showed that urea application caused a number of differentially expressed transcripts with several downregulated unigenes related to basic enzymes and several upregulated unigenes involved in stress resistance. The knockdown of a metalloproteinase gene caused a significant decrease in egg production, and the silencing of a carboxylesterase gene significantly reduced both the egg production and egg hatchability. Taken together, the present study found that urea application reduced P. pseudoannulata reproduction ability and the negative impact partially resulted from the downregulation of certain basic enzyme genes. The study provided a fresh view of fertilizers on beneficial arthropods with great potential in the protection of P. pseudoannulata in fields. Title: Combined toxicity of micro/nano scale polystyrene plastics and ciprofloxacin to Corbicula fluminea in freshwater sediments Guo X, Cai Y, Ma C, Han L, Yang Z Ref: Sci Total Environ, 789:147887, 2021 : PubMed ESTHER: Guo_2021_Sci.Total.Environ_789_147887 PubMedSearch: Guo 2021 Sci.Total.Environ 789 147887 PubMedID: 34051493 Abstract Plastic pollution has become a global environmental threat, and its potential to affect the bioavailability and toxicity of pharmaceuticals to aquatic organism are of growing concern. However, little is known regarding the combined toxicity of micro/nano-plastics and pharmaceuticals to benthic organisms in sediments. Thus, we employed a freshwater benthic bivalve, Corbicula fluminea (C. fluminea), to investigate the individual and co-toxicity of model plastics, microscopic fluorescent polystyrene (PS) (PS nano-plastic (PS-NP) and PS micro-plastic (PS-MP), 80 nm and 6 microm, respectively) and the common antibiotic ciprofloxacin (CIP) in formulated sediments. Our results suggest that oxidative damage and neurotoxicity were confirmed to occur in C. fluminea in all the treatments. The oxidative damage in the digestive glands reduced the clam ability to scavenge free radicals, causing severe tissue damage to the digestive glands of C. fluminea. Filtration rates of C. fluminea were significantly decreased in a concentration-dependent manner across all the treatments, which might be due to the inhibition of acetylcholinesterase activities. Interactions between CIP and micro/nano-plastic were observed, whereby the presence of PS decreased the toxicity of CIP in the digestive glands but aggravated the C. fluminea siphoning inhibition rate in the nano-plastic co-treatments group; in addition, the CIP toxicity to C. fluminea decreased because that the concentration of free dissolved CIP was lowered by micro/nano-PS. Taken together, the current study could contribute greatly to evaluating the ecological risk of CIP and PS in aquatic environments and sheds light on potential issues of food safety caused by both emerging pollutants. Title: Expression of an alkaline feruloyl esterases from thermophilic Chaetomium thermophilum and its boosting effect on delignification of pulp Hou Y, Yang Z, Yin Y, Meng Z, Wang J, Zhao T, Yang Q Ref: Enzyme Microb Technol, 150:109859, 2021 : PubMed ESTHER: Hou_2021_Enzyme.Microb.Technol_150_109859 PubMedSearch: Hou 2021 Enzyme.Microb.Technol 150 109859 PubMedID: 34489049 Abstract Exploration of feruloyl esterase (FAE) with the resistance to heat and alkali conditions in biobleaching process to improve the separation efficiency of lignocellulose is the key to achieving green papermaking. Herein, we expressed FAEB of C. thermophilum and obtained a thermostable alkaline FAE that can effectively promote the removal of lignin from pulp. The faeB gene was successfully obtained through genomic Blast strategy and high-efficiency expressed under the control of strong alcohol oxidase promoter in Pichia pastoris. The recombinant CtFAEB has an optimal temperature of 65 degreesC and pH of 7.0. After treated at 65 degreesC for 1 h, CtFAEB can still retain 63.21 % of its maximum activity, showing a good thermal stability. In addition, the recombinant CtFAEB has broad pH stability and can retain about 56 % of the maximum activity even at pH 11.0. Compared with the effect of mesophilic FAE, pretreatment with thermostable CtFAEB can promote the delignification by laccase and alkaline hydrogen peroxide from the pulp at 70 degreesC and pH 9.0. Alignment of the protein sequences of CtFAEB and mesophilic FAE suggested that the percentage of amino acids that easily form alpha helix in CtFAEB increases, which enhances its structural rigidity and thereby improves its thermal stability and alkali tolerance. Our study provides an effective method to obtain thermostable and alkaline FAEs, which will promote its application in biobleaching and other biorefining industries. Title: Identification of NDRG Family Member 4 (NDRG4) and CDC28 Protein Kinase Regulatory Subunit 2 (CKS2) as Key Prognostic Genes in Adrenocortical Carcinoma by Transcriptomic Analysis Yang Z, Cheng H, Zhang Y, Zhou Y Ref: Med Sci Monit, 27:e928523, 2021 : PubMed ESTHER: Yang_2021_Med.Sci.Monit_27_e928523 PubMedSearch: Yang 2021 Med.Sci.Monit 27 e928523 PubMedID: 33667214 Gene_locus related to this paper: human-NDRG4 Abstract BACKGROUND Adrenocortical carcinoma (ACC) is an aggressive cancer with heterogeneous outcomes. In this study, we aimed to investigate genomic and prognostic features of ACC. MATERIAL AND METHODS Clinical, pathologic, and transcriptomic data from 2 independent datasets derived from ACC samples (TCGA-ACC dataset, GEO-GSE76021 dataset) were collected. Weighted gene co-expression network analysis (WGCNA) and survival analyses were performed to identify prognostic genes. Pathway analysis was performed for mechanistic analysis. xCell deconvolution was performed for tumor microenvironment analysis. RESULTS In the TCGA-ACC cohort, WGCNA identified a prognostic module of 5408 genes. Differential expression analysis identified 1969 genes that differed in expression level between long-term and short-term survivors. Univariate Cox regression model analysis identified 8393 genes with prognostic value. The intersection of these gene sets included 820 prognostic genes. Similar protocols were performed for the GSE76021 dataset, and 5 candidate genes were identified. Further intersection of these genes finally identified NDRG4 and CKS2 as key prognostic genes. Multivariate Cox regression model analysis validated the prognostic value of NDRG4 (HR=0.61, 95% CI 0.46-0.80) and CKS2 (HR=2.52, 95% CI 1.38-4.60). Moreover, NDRG4 and CKS2 expression predicted survival in patients treated with mitotane (P<0.001). Further mechanism exploration found an association between CKS2 and DNA mismatch repair pathways. Moreover, NDRG4 positively correlated with CD8 T cell infiltration, while CKS2 negatively correlated with it. CONCLUSIONS We identified NDRG4 and CKS2 expression as key prognostic genes in ACC, which may help in risk stratification of ACC. Moreover, a close relationship was found between CKS2 and mismatch repair pathways. Moreover, immune cell infiltration differed according to NDRG4 and CKS2 expression. Title: Network Pharmacology-Based Study of the Underlying Mechanisms of Huangqi Sijunzi Decoction for Alzheimer's Disease Zhang W, Lv M, Shi Y, Mu Y, Yao Z, Yang Z Ref: Evid Based Complement Alternat Med, 2021:6480381, 2021 : PubMed ESTHER: Zhang_2021_Evid.Based.Complement.Alternat.Med_2021_6480381 PubMedSearch: Zhang 2021 Evid.Based.Complement.Alternat.Med 2021 6480381 PubMedID: 34650613 Abstract BACKGROUND: Huangqi Sijunzi decoction (HQSJZD) is a commonly used conventional Chinese herbal medicine prescription for invigorating Qi, tonifying Yang, and removing dampness. Modern pharmacology and clinical applications of HQSJZD have shown that it has a certain curative effect on Alzheimer's disease (AD). METHODS: The active components and targets of HQSJZD were searched in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The genes corresponding to the targets were retrieved using UniProt and GeneCard database. The herb-compound-target network and protein-protein interaction (PPI) network were constructed by Cytoscape. The core targets of HQSJZD were analysed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The main active compounds of HQSJZD were docked with acetylcholinesterase (AChE). In vitro experiments were conducted to detect the inhibitory and neuroprotective effects of AChE. RESULTS: Compound-target network mainly contained 132 compounds and 255 corresponding targets. The main compounds contained quercetin, kaempferol, formononetin, isorhamnetin, hederagenin, and calycosin. Key targets contained AChE, PTGS2, PPARG, IL-1B, GSK3B, etc. There were 1708 GO items in GO enrichment analysis and 310 signalling pathways in KEGG, mainly including the cAMP signalling pathway, the vascular endothelial growth factor (VEGF) signalling pathway, serotonergic synapses, the calcium signalling pathway, type II diabetes mellitus, arginine and proline metabolism, and the longevity regulating pathway. Molecular docking showed that hederagenin and formononetin were the top 2 compounds of HQSJZD, which had a high affinity with AChE. And formononetin has a good neuroprotective effect, which can improve the oxidative damage of nerve cells. CONCLUSION: HQSJZD was found to have the potential to treat AD by targeting multiple AD-related targets. Formononetin and hederagenin in HQSJZD may regulate multiple signalling pathways through AChE, which might play a therapeutic role in AD. Title: Novel Cinnamoylated Flavoalkaloids Identified in Tea with Acetylcholinesterase Inhibition Effect Gaur R, Ke JP, Zhang P, Yang Z, Bao GH Ref: Journal of Agricultural and Food Chemistry, :, 2020 : PubMed ESTHER: Gaur_2020_J.Agric.Food.Chem__ PubMedSearch: Gaur 2020 J.Agric.Food.Chem PubMedID: 32053361 Abstract 3-O-cinnamoylepicatechin (1) was synthesized along with four flavoalkaloids, (-)-6-(5'''S)-N-ethyl-2-pyrrolidinone-3-O-cinnamoylepicatechin (2), (-)-6-(5'''R)-N-ethyl-2-pyrrolidinone--3-O-cinnamoylepicatechin (3), (-)-8-(5'''S)-N-ethyl-2-pyrrolidinone-3-O-cinnamoylepicatechin (4), and (-)-8-(5'''R)-N-ethyl-2-pyrrolidinone-3-O-cinnamoylepicatechin (5) via esterification of epicatechin followed by phenolic Mannich reaction of 1 with theanine in the presence of heat. The new compounds 1-5 were detected in leaves of three tea cultivars, Fuding-Dabai, Huangjingui, and Zimudan with the help of ultra performance liquid chromatography hyphenated with photodiode array detector and electrospray ionization high resolution mass spectrometry (UPLC-PDA-ESI-HRMS), suggesting that they are naturally occurring in tea leaves. The structures of the novel natural products were characterized by one and two dimensional nuclear magnetic resonance (1D and 2D NMR) and mass spectroscopy. Compounds 1-5 were then evaluated for their acetylcholinesterase (AChE) inhibitory effect (IC50 = 0.12 - 1.02 muM). The availability of the synthesized epicatechin derivatives 1-5 via synthetic route enabled the first unequivocal identification of these derivatives as tea secondary metabolites and made it possible to determine their content in the tea material as well as the diverse bioactivities. Title: Correlation analysis between CARMEN variants and alcohol-induced osteonecrosis of the femoral head in the Chinese population Guo Y, Cao Y, Gong S, Zhang S, Hou F, Zhang X, Hu J, Yang Z, Yi J and Song J <2 more author(s)> Guo Y, Cao Y, Gong S, Zhang S, Hou F, Zhang X, Hu J, Yang Z, Yi J, Luo D, Chen X, Song J (- 2) Ref: BMC Musculoskelet Disord, 21:547, 2020 : PubMed ESTHER: Guo_2020_BMC.Musculoskelet.Disord_21_547 PubMedSearch: Guo 2020 BMC.Musculoskelet.Disord 21 547 PubMedID: 32799824 Abstract BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a complicated disease associated with trauma, hormone abuse and excessive alcohol consumption. Polymorphisms of long non-coding RNAs have been also linked with the development of ONFH. Our research aimed to explore the relationship between CARMEN (Cardiac Mesoderm Enhancer-Associated Non-Coding RNA) variants and ONFH risk. METHODS: Our study used Agena MassARRAY Assay to genotype 6 selected single nucleotide polymorphisms (SNPs) in 731 participants (308 alcohol-induced ONFH patients and 423 controls). We used odds ratios (ORs) and 95% confidence intervals (CIs) to calculate the effect of gene polymorphisms on the occurrence of alcohol-induced ONFH by logistic regression analysis and haplotype analysis. RESULTS: Our overall analysis illustrated that rs13177623 and rs12654195 had an association with a reduced risk of ONFH after adjustment for age and gender. We also found that rs13177623, rs12654195 and rs11168100 were associated with a decreased susceptibility to alcohol-induced ONFH in people <=45 years. In addition, the necrotic sites stratification analysis showed that rs12654195 was only found to be related to alcohol-induced ONFH risk in the recessive model. In patients with different clinical stages, rs353300 was observed to be associated with a higher incidence of ONFH. Individuals with different genotypes of rs13177623, rs12654195 and rs11168100 had significantly different clinical parameters (cholinesterase, globulin, percentage of neutrophils and the absolute value of lymphocytes). CONCLUSIONS: Our data provided new light on the association between CARMEN polymorphisms and alcohol-induced ONFH risk in the Chinese Han population. Title: In Vivo Enzyme Entrapment in a Protein Crystal Heater BS, Yang Z, Lee MM, Chan MK Ref: Journal of the American Chemical Society, :, 2020 : PubMed ESTHER: Heater_2020_J.Am.Chem.Soc__ PubMedSearch: Heater 2020 J.Am.Chem.Soc PubMedID: 32407637 Abstract Cry3Aa is a protein that forms crystals naturally in the bacterium Bacillus thuringiensis. Here we report that coexpression of Cry3Aa and a Proteus mirabilis lipase without recombinant fusion results in the efficient passive entrapment of the lipase within the nanoporous channels of the resulting crystals. This Cry3Aa crystal-mediated entrapment provides multiple benefits to the lipase including a high enzyme loading, significantly improved thermostability, increased proteolytic resistance, and the ability to be utilized as a recyclable biodiesel catalyst. These characteristics, along with its greatly simplified method of isolation, highlight the potential of Cry3Aa crystal-mediated enzyme entrapment for use in biocatalysis and other biotechnological applications. Title: Improved production of recombinant Rhizomucor miehei lipase by coexpressing protein folding chaperones in Pichia pastoris, which triggered ER stress Huang J, Zhao Q, Chen L, Zhang C, Bu W, Zhang X, Zhang K, Yang Z Ref: Bioengineered, 11:375, 2020 : PubMed ESTHER: Huang_2020_Bioengineered_11_375 PubMedSearch: Huang 2020 Bioengineered 11 375 PubMedID: 32175802 Gene_locus related to this paper: rhimi-lipas Abstract Rhizomucor miehei lipase (RML) is a biocatalyst that widely used in laboratory and industrial. Previously, RML with a 70-amino acid propeptide (pRML) was cloned and expressed in P. pastoris. Recombinant strains with (strain containing 4-copy prml) and without ER stress (strain containing 2-copy prml) were obtained. However, the effective expression of pRML in P. pastoris by coexpressing ER-related elements in pRML-produced strain with or without ER stress has not been reported to date. In this study, an efficient way to produce functional pRML was explored in P. pastoris. The coexpression of protein folding chaperones, including PDI and ERO1, in different strains with or without ER stress, was investigated. PDI overexpression only increased pRML production in 4-copy strain from 705 U/mL to 1430 U/mL because it alleviated the protein folded stress, increased the protein concentration from 0.56 mg/mL to 0.65 mg/mL, and improved enzyme-specific activity from 1238 U/mg to 2186 U/mg. However, PDI coexpression could not improve pRML production in the 2-copy strain because it increased protein folded stress, while ERO1 coexpression in the two strains all had a negative effect on pRML expression. We also investigated the effect of the propeptide on the substrate specificity and the condition for pRML enzyme powder preparation. Results showed that the relative activity exceeded 80% when the substrates C8-C10 were detected at 35 degrees C and pH 6, and C8-C12 at 45 degrees C and pH 8. The optimal enzyme powder preparation pH was 7, and the maximum recovery rate for pRML was 73.19%. Title: Tacrine accelerates spatial long-term memory via improving impaired neural oscillations and modulating GAD isomers including neuro-receptors in the hippocampus of APP/PS1 AD mice Kumari E, Li K, Yang Z, Zhang T Ref: Brain Research Bulletin, :, 2020 : PubMed ESTHER: Kumari_2020_Brain.Res.Bull__ PubMedSearch: Kumari 2020 Brain.Res.Bull PubMedID: 32473192 Abstract Tacrine (Amino tetrahydroacridine hydrochloride hydrate) is a non-competitive and reversible inhibitor of acetylcholine esterase, and butylcholinesterase. Alzheimer's disease (AD) shows multiple types of pathological pathway in which cholinergic neuron deficiency is 95 % popular and the oldest pathological mechanism. However, the effect of tacrine on the hippocampal dependent memory is not yet known. In this study, we did verify that tacrine induced recovery of the specific pattern associated memory along with long-term memory through the improvement in the pattern of neural oscillation from deficits condition in the hippocampus of 6th month old AD mice. Our results showed that tacrine improved the performance of Morris water maze related spatial cognitive functions, and enhanced LTP in AD-TAC mice. Furthermore, our results implied that tacrine strongly improve the patterns of neural oscillations, and hippocampal synaptic plasticity in the 6th month old APP-PS1 double transgenic AD-TAC mice via changing the theta and alpha power spectra including with the improvement in theta, alpha and gamma synchronization. Moreover, tacrine generated the improvement in the theta cross spectra, theta-gamma phase-phase synchronization and theta-gamma phase-amplitude coupling. Besides, the data represented that tacrine accelerated the expression of NR2B, SYP and GAD65 while it caused deceleration on the expression of GAD67 neurotransmitter and Abeta. Thus, our results infer that tacrine works as a strong causative agent for improving the specific pattern-associated spatial long-term memory in the AD mice without showing any side effect. Title: Effect of Solvent on Acyl Migration of 2-Monoacylglycerols in Enzymatic Ethanolysis Wang X, Zhao X, Yang Z, Wang T Ref: Journal of Agricultural and Food Chemistry, 68:12358, 2020 : PubMed ESTHER: Wang_2020_J.Agric.Food.Chem_68_12358 PubMedSearch: Wang 2020 J.Agric.Food.Chem 68 12358 PubMedID: 33084305 Abstract Acyl migration occurs in many reactions and is the main obstacle for structured lipid synthesis. In this study, 2-monoacylglycerol (2-MAG) was prepared by enzymatic ethanolysis in three different media to evaluate the effect of environment on product composition. The contents of 2-MAG obtained in ethanol, hexane + ethanol, and t-butanol + ethanol systems were 30.6, 15.7, and 32.4%, respectively, after 3 h reaction. Afterward, the acyl migration kinetics of 2-MAG were studied in solvent and solventless systems without the use of lipase. Results indicate that 2-MAG in the solventless system had the highest acyl migration rate. The isomerization was efficiently prevented by the use of polar solvents, especially t-butanol. The rate constants were shown to be the highest and activation energy values were the lowest in solventless systems. The novel finding in this study was that solvent had inhibitory effect on 2-MAG isomerization, but the nonpolar hexane had the lowest inhibition of acyl migration compared to other solvents. Title: Identification, characterization and expression analyses of cholinesterases genes in Yesso scallop (Patinopecten yessoensis) reveal molecular function allocation in responses to ocean acidification Xing Q, Liao H, Peng C, Zheng G, Yang Z, Wang J, Lu W, Huang X, Bao Z Ref: Aquat Toxicol, 231:105736, 2020 : PubMed ESTHER: Xing_2020_Aquat.Toxicol_231_105736 PubMedSearch: Xing 2020 Aquat.Toxicol 231 105736 PubMedID: 33422860 Gene_locus related to this paper: mizye-a0a210qls6, mizye-a0a210qis3, mizye-a0a210qg00, mizye-a0a210r5n9, mizye-a0a210qbv2, mizye-a0a210pu25, mizye-a0a210ptr6, mizye-a0a210ptv1, mizye-a0a210ptq0, mizye-P021348901.2 Abstract Cholinesterases are key enzymes in central and peripheral cholinergic nerve system functioning on nerve impulse transmission in animals. Though cholinesterases have been identified in most vertebrates, the knowledge about the variable numbers and multiple functions of the genes is still quite meagre in invertebrates, especially in scallops. In this study, the complete cholinesterase (ChE) family members have been systematically characterized in Yesso scallop (Patinopecten yessoensis) via whole-genome scanning through in silico analysis. Ten ChE family members in the genome of Yesso scallop (designated PyChEs) were identified and potentially acted to be the largest number of ChE in the reported species to date. Phylogenetic and protein structural analyses were performed to determine the identities and evolutionary relationships of these genes. The expression profiles of PyChEs were determined in all developmental stages, in healthy adult tissues, and in mantles under low pH stress (pH 6.5 and 7.5). Spatiotemporal expression suggested the ubiquitous functional roles of PyChEs in all stages of development, as well as general and tissue-specific functions in scallop tissues. Regulation expressions revealed diverse up- and down-regulated expression patterns at most time points, suggesting different functional specialization of gene superfamily members in response to ocean acidification (OA). Evidences in gene number, phylogenetic relationships and expression patterns of PyChEs revealed that functional innovations and differentiations after gene duplication may result in altered functional constraints among PyChEs gene clusters. Collectively, our results provide the potential clues that the selection pressures coming from the environment were the potential inducement leading to function allocation of ChE family members in scallop. Title: Activation of cholinergic anti-inflammatory pathway involved in therapeutic actions of alpha-mangostin on lipopolysaccharide-induced acute lung injury in rats Yang Z, Yin Q, Olatunji OJ, Li Y, Pan S, Wang DD, Zuo J Ref: Int J Immunopathol Pharmacol, 34:2058738420954941, 2020 : PubMed ESTHER: Yang_2020_Int.J.Immunopathol.Pharmacol_34_2058738420954941 PubMedSearch: Yang 2020 Int.J.Immunopathol.Pharmacol 34 2058738420954941 PubMedID: 32886564 Abstract INTRODUCTION: Alpha-mangostin (MAN) possesses a wide variety of pharmacological effects. In this study, we investigated its effect on cholinergic anti-inflammatory pathway (CAP), and tested if CAP regulation was involved in the therapeutic action on acute lung injury (ALI). METHODS: Male Sprague Dawley rats were pre-treated with MAN (40 mg/kg) for 3 days and ALI was induced with an intraperitoneal injection of lipopolysaccharide (LPS). Certain rats received monolateral vagotomy or sham surgery. The effects on inflammatory reactions and relevant pathways in ALI rats or LPS pre-treated RAW 264.7 cells were investigated by histological, immunohistochemical, immunoblotting, RT-qPCR, and immunofluorescence assays, while levels of proinflammatory cytokines, acetylcholine (Ach) and the enzymatic activity of acetylcholinesterase (AchE) were determined by corresponding quantitative kits. RESULTS: Oral administration of MAN reduced the severity of ALI, while vagotomy surgery antagonized this effect. MAN restored the decline in alpha7 nicotinic acetylcholine receptor (alpha7nAchR) in the lungs of ALI rats, and promoted the expression of alpha7nAchR and choline acetyltransferase (CHAT) in RAW 264.7 cells. Although AchE expression was barely affected by MAN at 5 mug/ml, its catalytic activity was reduced by almost 95%. Extracellular rather than intracellular Ach was notably raised shortly after MAN treatment. Furthermore, MAN at 5 mug/ml effectively inhibited LPS-induced increase in phosphorylation and nucleus translocation of p65 subunit, and secretion of TNF-alpha and IL-1beta, which was then offset by methyllycaconitine citrate hydrate. CONCLUSION: MAN activated CAP by increasing peripheral Ach and up-regulating alpha7nAchR expression, which eventually led to NF-kappaB inhibition and remission of acute inflammations. Title: A new prognostic factor of breast cancer: High carboxyl ester lipase expression related to poor survival Cui Y, Jiao Y, Wang K, He M, Yang Z Ref: Cancer Genet, 239:54, 2019 : PubMed ESTHER: Cui_2019_Cancer.Genet_239_54 PubMedSearch: Cui 2019 Cancer.Genet 239 54 PubMedID: 31561066 Abstract OBJECTIVE: The enzyme carboxyl ester lipase (CEL), known as bile salt-dependent lipase (BSDL) or bile salt-stimulated lipase (BSSL), is mainly expressed in pancreatic acinar cells and lactating mammary glands. To investigate the link between CEL expression of breast cancer (BC) tissues and the survival of BC patients by analyzing The Cancer Genome Atlas Breast Carcinoma (TCGA-BRCA) level 3 data. METHODS: The clinical information and RNA-sequencing (RNA-Seq) expression data were downloaded from TCGA. Patients were divided into a high CEL expression group and a low CEL expression group using the optimal cutoff value (5.611) identified from the ROC curve. Chi-square test and Fisher exact test were used to find the correlation between the expression of CEL and clinicopathologic features. To assess the diagnostic capability, the receiver operating characteristic (ROC) curve of CEL was drawn. The survival differences between high and low CEL expression groups were compared by Cox regression analysis. Log-rank test was applied to the calculation of p values and the comparison of the Kaplan-Meier curves. Furthermore, Gene Expression Omnibus (GEO) datasets were used for external data validation. RESULTS: Analysis of 1104 cases of tumor data showed that CEL was over-expressed in breast cancer. There were relationships between high CEL expression and clinicopathologic features. The high CEL expression group had a lower survival. By analyzing the area under the ROC curve (AUC) of CEL, it was found to have a limited diagnostic capability. CEL expression may be an independent prognostic factor for breast cancer survival through the multivariate analysis. The validation in GEO datasets also showed that CEL expression was higher in breast tumor tissues than in normal breast tissues. High CEL expression was associated with the poor overall survival of breast cancer. CONCLUSIONS: High CEL expression may be an independent prognostic factor for the poor survival of breast cancer. Title: Lipase-catalyzed synthesis of ethyl (R)-2-benzyloxy-2-isopropylhydrogenmalonate: a useful combination of chemical synthesis with enzymatic methods Ding J, Yang Z, Zhao Y, Fang W, Lu Q Ref: Biosci Biotechnol Biochem, :1, 2019 : PubMed ESTHER: Ding_2019_Biosci.Biotechnol.Biochem__1 PubMedSearch: Ding 2019 Biosci.Biotechnol.Biochem 1 PubMedID: 30654732 Abstract Ethyl (R)-2-benzyloxy-2-isopropylhydrogenmalonate is a key intermediate for the synthesis of the side chain in ergopeptines. In this work, we adopted a method to prepare enantiomerically pure title monoester via immobilized Candida antarctica lipase B (Novozym 435)-catalyzed hydrolysis of the corresponding diester. Title: Different construction strategies affected on the physiology of Pichia pastoris strains highly expressed lipase by transcriptional analysis of key genes Huang J, Wang Q, Bu W, Chen L, Yang Z, Zheng W, Li Y, Li J Ref: Bioengineered, 10:150, 2019 : PubMed ESTHER: Huang_2019_Bioengineered_10_150 PubMedSearch: Huang 2019 Bioengineered 10 150 PubMedID: 31079540 Abstract We demonstrated previously that expression of Rhizomucor miehei lipase (RML) in Pichia pastoris could be significantly increased by addition of gene propeptide, optimized signal peptide codons and manipulation of gene dosage. In this study, effects of various strategies on the protein synthesis and secretion pathways were analyzed. Using nine strains previously constructed, we evaluated cell culture properties, enzymatic activities, and analyzed transcriptional levels of nine genes involved in protein synthesis and secretion pathways by qPCR. We observed that (i) Addition of propeptide decreased lipase folding stress by down-regulated four UPR-related genes. (ii) Signal peptide codons optimization had no effect on host with no change in the nine detected genes. (iii) Folding stress and limited transport capacity produced when rml gene dosage exceed 2. Different limiting factors on lipase expression in strains with different construction strategies were identified. This study provides a theoretical basis for further improving RML by transforming host. Title: Enantioselective Hydrolysis of Styrene Oxide and Benzyl Glycidyl Ether by a Variant of Epoxide Hydrolase from Agromyces mediolanus Jin H, Li Y, Zhang Q, Lin S, Yang Z, Ding G Ref: Mar Drugs, 17:, 2019 : PubMed ESTHER: Jin_2019_Mar.Drugs_17_ PubMedSearch: Jin 2019 Mar.Drugs 17 PubMedID: 31226863 Abstract Enantiopure epoxides are versatile synthetic intermediates for producing optically active pharmaceuticals. In an effort to provide more options for the preparation of enantiopure epoxides, a variant of the epoxide hydrolase (vEH-Am) gene from a marine microorganism Agromyces mediolanus was synthesized and expressed in Escherichia coli. Recombiant vEH-Am displayed a molecular weight of 43 kDa and showed high stability with a half-life of 51.1 h at 30 degrees C. The purified vEH-Am exhibited high enantioselectivity towards styrene oxide (SO) and benzyl glycidyl ether (BGE). The vEH-Am preferentially converted (S)-SO, leaving (R)-SO with the enantiomeric excess (ee) >99%. However, (R)-BGE was preferentially hydrolyzed by vEH-Am, resulting in (S)-BGE with >99% ee. To investigate the origin of regioselectivity, the interactions between vEH-Am and enantiomers of SO and BGE were analyzed by molecular docking simulation. In addition, it was observed that the yields of (R)-SO and (S)-BGE decreased with the increase of substrate concentrations. The yield of (R)-SO was significantly increased by adding 2% (v/v) Tween-20 or intermittent supplementation of the substrate. To our knowledge, vEH-Am displayed the highest enantioselectivity for the kinetic resolution of racemic BGE among the known EHs, suggesting promising applications of vEH-Am in the preparation of optically active BGE. Title: Identification and Analysis of Chemical Constituents and Rat Serum Metabolites in Lycopodium clavatum Using UPLC-Q-TOF/MS Combined with Multiple Data-Processing Approaches Li X, Kang M, Ma N, Pang T, Zhang Y, Jin H, Yang Z, Song L Ref: Evid Based Complement Alternat Med, 2019:5165029, 2019 : PubMed ESTHER: Li_2019_Evid.Based.Complement.Alternat.Med_2019_5165029 PubMedSearch: Li 2019 Evid.Based.Complement.Alternat.Med 2019 5165029 PubMedID: 31354854 Abstract Lycopodium clavatum is a dry whole grass of Lycopodium japonicum Thunb.; it has been extensively used to anti-inflammatory, antioxidant, and antimicrobial actions and inhibits acetylcholinesterase activity. However, it lacks further compounds research of Lycopodium clavatum in vivo and in vitro. In this work, a rapid method was established using the ultra high performance liquid chromatography with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS) combined with multiple data-processing approaches for compounds analysis of Lycopodium clavatum in vitro and in vivo. Finally, 30 peaks were characterized in 75% ethanol extract of Lycopodium clavatum and 17 peaks were characterized in rat plasma that including 12 prototype compounds and 5 metabolites. Methylation and demethylation are the main transformation reactions of Lycopodium clavatum in rat serum. This work could be helpful for understanding the complex compounds of Lycopodium clavatum and further analyzing the pharmacological studies of active compounds. Title: Catalytic Hydrolysis Mechanism of Cocaine by Human Carboxylesterase 1: An Orthoester Intermediate Slows Down the Reaction Yan M, Zhang Z, Liu Z, Zhang C, Zhang J, Fan S, Yang Z Ref: Molecules, 24:, 2019 : PubMed ESTHER: Yan_2019_Molecules_24_ PubMedSearch: Yan 2019 Molecules 24 PubMedID: 31717501 Gene_locus related to this paper: human-CES1 Abstract Human carboxylesterase 1 (hCES1) is a major carboxylesterase in the human body and plays important roles in the metabolism of a wide variety of substances, including lipids and drugs, and therefore is attracting more and more attention from areas including lipid metabolism, pharmacokinetics, drug-drug interactions, and prodrug activation. In this work, we studied the catalytic hydrolysis mechanism of hCES1 by the quantum mechanics computation method, using cocaine as a model substrate. Our results support the four-step theory of the esterase catalytic hydrolysis mechanism, in which both the acylation stage and the deacylation stage include two transition states and a tetrahedral intermediate. The roles and cooperation of the catalytic triad, S221, H468, and E354, were also analyzed in this study. Moreover, orthoester intermediates were found in hCES1-catalyzed cocaine hydrolysis reaction, which significantly elevate the free energy barrier and slow down the reaction. Based on this finding, we propose that hCES1 substrates with beta-aminocarboxylester structure might form orthoester intermediates in hCES1-catalyzed hydrolysis, and therefore prolong their in vivo half-life. Thus, this study helps to clarify the catalytic mechanism of hCES1 and elucidates important details of its catalytic process, and furthermore, provides important insights into the metabolism of hCES1 substrates and drug designing. Title: SNHG20/miR-140-5p/NDRG3 axis contributes to 5-fluorouracil resistance in gastric cancer Yu J, Shen J, Qiao X, Cao L, Yang Z, Ye H, Xi C, Zhou Q, Wang P, Gong Z Ref: Oncol Lett, 18:1337, 2019 : PubMed ESTHER: Yu_2019_Oncol.Lett_18_1337 PubMedSearch: Yu 2019 Oncol.Lett 18 1337 PubMedID: 31423195 Gene_locus related to this paper: human-NDRG3 Abstract 5-fluorouracil (5-FU)-based chemotherapy is the first line treatment for advanced gastric cancer. However, the effectiveness of 5-FU is limited by drug resistance. The N-myc downstream-regulated gene, family member 3 (NDRG3) is a member of the NDRG family and has been implicated in numerous types of cancer. However, the role of NDRG3 in gastric cancer remains unclear. In the present study, NDRG3 mRNA expression in gastric cancer and adjacent normal tissues was analyzed using the Gene Expression Profiling Interactive Analysis web tool. NDRG3 expression was silenced using short hairpin RNAs to examine the effect of NDRG3 on the growth of gastric cancer cells. Potential regulators of NDRG3 were identified using the TargetScan and MicroRNA tools and verified by a luciferase assay and reverse transcription-quantitative PCR analysis. The current study demonstrated that NDRG3 was upregulated in gastric cancer specimens and promoted cell proliferation in gastric cancer cell lines. Furthermore, the present study revealed that the small nucleolar RNA host gene 20 (SNHG20)/microRNA (miR)-140-5p signaling pathway may regulate the expression of NDRG3. SNHG20 was revealed to be involved in mediating resistance to 5-FU in gastric cancer cell lines via NDRG3. In conclusion, the results of the present study suggest that the SNHG20/miR-140-5p/NDRG3 axis may be involved in mediating resistance to 5-FU in gastric cancer. Title: Design, synthesis and evaluation of chalcone Mannich base derivatives as multifunctional agents for the potential treatment of Alzheimer's disease Zhang X, Song Q, Cao Z, Li Y, Tian C, Yang Z, Zhang H, Deng Y Ref: Bioorg Chem, 87:395, 2019 : PubMed ESTHER: Zhang_2019_Bioorg.Chem_87_395 PubMedSearch: Zhang 2019 Bioorg.Chem 87 395 PubMedID: 30921741 Abstract A series of chalcone Mannich base derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease based on the multi-target directed ligands design strategy. In vitro assays demonstrated that most of the derivatives exerted potent selective inhibitory potency on AChE with good multifunctional properties. Among them, representative compound 7c exhibited moderate inhibitory potency for EeAChE (IC50=0.44muM) and MAO-B inhibition (IC50=1.21muM), good inhibitory effect on self-induced Abeta1-42 aggregation (55.0%, at 25muM), biometal chelating property, moderate antioxidant activity with a value 1.93-fold of Trolox. Moreover, both kinetic analysis of AChE inhibition and molecular modeling study revealed that 7c showed a mixed-type inhibition, binding simultaneously to CAS and PAS of AChE. In addition, 7c also displayed high BBB permeability. These properties indicated 7c may be a promising multifunctional agent for the treatment of AD. Title: CXCL5, the upregulated chemokine in patients with uterine cervix cancer, in vivo and in vitro contributes to oncogenic potential of Hela uterine cervix cancer cells Feng X, Zhang D, Li X, Ma S, Zhang C, Wang J, Li Y, Liang L, Zhang P and Wang W <7 more author(s)> Feng X, Zhang D, Li X, Ma S, Zhang C, Wang J, Li Y, Liang L, Zhang P, Qu Y, Zhang Z, Yang Z, Xiang Y, Zhang W, Wang S, Shao W, Wang W (- 7) Ref: Biomed Pharmacother, 107:1496, 2018 : PubMed ESTHER: Feng_2018_Biomed.Pharmacother_107_1496 PubMedSearch: Feng 2018 Biomed.Pharmacother 107 1496 PubMedID: 30257367 Abstract CXCL5 is showed a surprisingly elevated profile and implicated in tumorigenesis in several tumors. However, the expression and function of CXCL5 in uterine cervix cancer (UCC) remain largely unknown. The current study aimed to elucidate the expression pattern of CXCL5 in human UCC tissues and Hela cervix cancer cell, as well as its functions in Hela cells. Our data showed that CXCL5 and its receptor CXCR2 were expressed by Hela uterine cervix cancer cells. CXCL5 was upregulated in UCC tissues, and its overexpression was positively correlated with age, but did not correlate with clinical stages and tumor infiltration. Exogenous administration of CXCL5 and CXCL5 overexpression contributed to proliferation and migration activities of Hela cells in vitro, consistent with this, CXCL5 overexpression also promoted growth of Hela cells in a nude mouse xenograft model. At the gene level, CXCL5 overexpression regulated the expression of tumor-related genes including ERK, p-ERK, AKT, p-AKT, DIABOL, NUMB, NDRG3 and CXCR2. Taken together, CXCL5 may contribute to a dominant role in UCC progression and sever as a potential molecular therapeutic target for UCC. Title: Coumarin-dithiocarbamate hybrids as novel multitarget AChE and MAO-B inhibitors against Alzheimer's disease: Design, synthesis and biological evaluation He Q, Liu J, Lan JS, Ding J, Sun Y, Fang Y, Jiang N, Yang Z, Sun L and Xie SS <1 more author(s)> He Q, Liu J, Lan JS, Ding J, Sun Y, Fang Y, Jiang N, Yang Z, Sun L, Jin Y, Xie SS (- 1) Ref: Bioorg Chem, 81:512, 2018 : PubMed ESTHER: He_2018_Bioorg.Chem_81_512 PubMedSearch: He 2018 Bioorg.Chem 81 512 PubMedID: 30245233 Abstract A series of new coumarin-dithiocarbamate hybrids were designed and synthesized as multitarget agents for the treatment of Alzheimer's disease. Most of them showed potent and clearly selective inhibition towards AChE and MAO-B. Among these compounds, compound 8f demonstrated the most potent inhibition to AChE with IC50 values of 0.0068muM and 0.0089muM for eeAChE and hAChE, respectively. Compound 8g was identified as the most potent inhibitor to hMAO-B, and it is also a good and balanced inhibitor to both hAChE and hMAO-B (0.114microM for hAChE; 0.101microM for hMAO-B). Kinetic and molecular modeling studies revealed that 8g was a dual binding site inhibitor for AChE and a competitive inhibitor for MAO-B. Further studies indicated that 8g could penetrate the BBB and exhibit no toxicity on SH-SY5Y neuroblastoma cells. More importantly, 8g did not display any acute toxicity in mice at doses up to 2500mg/kg and could reverse the cognitive dysfunction of scopolamine-induced AD mice. Overall, these results highlighted 8g as a potential multitarget agent for AD treatment and offered a starting point for design of new multitarget AChE/MAO-B inhibitors based on dithiocarbamate scaffold. Title: Efficient heterologous expression of an alkaline lipase and its application in hydrolytic production of free astaxanthin Huang J, Yang Z, Zhu R, Qian X, Wang Y, Li Y, Li J Ref: Biotechnol Biofuels, 11:181, 2018 : PubMed ESTHER: Huang_2018_Biotechnol.Biofuels_11_181 PubMedSearch: Huang 2018 Biotechnol.Biofuels 11 181 PubMedID: 29983744 Gene_locus related to this paper: penex-Q9HFW6 Abstract Background: Astaxanthin, a naturally occurring carotenoid pigment molecule, displays strong antioxidant, anti-cancer, and immunity-enhancing properties, and is often utilized in food, biomedical, cosmetic, and other industries. Free astaxanthin has better solubility than astaxanthin esters (Ast-E), and is a useful auxiliary ingredient in health foods and medicines. Our goal was to establish an improved enzymatic method for preparation of free astaxanthin from natural sources (e.g., the microalga Haematococcus pluvialis), to expand the potential applications of free astaxanthin. Results: The alkaline lipase gene proalip and its propeptide were cloned and successfully fusion-expressed in Pichia pastoris X-33. The recombinant lipase was termed Lipase-YH. Through optimization of culture conditions (medium formulation, pH, added methanol concentration), cell growth (OD600) and secreted enzyme activity respectively reached to 280 and 2050 U/mL in a 50-L autofermentor. Activity of Lipase-YH enzyme powder was about 40,000 U/g. Hydrolysis of Ast-E (extracted from H. pluvialis) by Lipase-YH occurred in aqueous phase, and reaction conditions were optimized based on emulsification method and enzyme/substrate ratio. The highest enzymatic reaction rate was observed for substrate concentration 200 mug/mL, with maximal free astaxanthin yield (80%) at 1 h, and maximal Ast-E hydrolysis rate 96%, as confirmed by TLC, HPLC, and mass spectroscopy. Conclusion: A novel, efficient enzymatic process was developed for production of free astaxanthin through hydrolysis of Ast-E. Lipase activity was enhanced, and production cost was greatly reduced. The unique structure of free astaxanthin allows linkage to various functional compounds, which will facilitate development of novel pharmaceutical and food products in future studies. Title: Discovery of novel 2,5-dihydroxyterephthalamide derivatives as multifunctional agents for the treatment of Alzheimer's disease Song Q, Li Y, Cao Z, Liu H, Tian C, Yang Z, Qiang X, Tan Z, Deng Y Ref: Bioorganic & Medicinal Chemistry, 26:6115, 2018 : PubMed ESTHER: Song_2018_Bioorg.Med.Chem_26_6115 PubMedSearch: Song 2018 Bioorg.Med.Chem 26 6115 PubMedID: 30470598 Abstract A series of 2,5-dihydroxyterephthalamide derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. In vitro assays demonstrated that most of the derivatives exhibited good multifunctional activities. Among them, compound 9d showed the best inhibitory activity against both RatAChE and EeAChE (IC50=0.56muM and 5.12muM, respectively). Moreover, 9d exhibited excellent inhibitory effects on self-induced Abeta1-42 aggregation (IC50=3.05muM) and Cu(2+)-induced Abeta1-42 aggregation (71.7% at 25.0muM), and displayed significant disaggregation ability to self- and Cu(2+)-induced Abeta1-42 aggregation fibrils (75.2% and 77.2% at 25.0muM, respectively). Furthermore, 9d also showed biometal chelating abilities, antioxidant activity, anti-neuroinflammatory activities and appropriate BBB permeability. These multifunctional properties highlight 9d as promising candidate for further studies directed to the development of novel drugs against AD. Title: Treatment of secondary brain injury by perturbing postsynaptic density protein-95-NMDA receptor interaction after intracerebral hemorrhage in rats Wang Z, Chen Z, Yang J, Yang Z, Yin J, Duan X, Shen H, Li H, Chen G Ref: Journal of Cerebral Blood Flow & Metabolism, :271678X18762637, 2018 : PubMed ESTHER: Wang_2018_J.Cereb.Blood.Flow.Metab__271678X18762637 PubMedSearch: Wang 2018 J.Cereb.Blood.Flow.Metab 271678X18762637 PubMedID: 29513122 Abstract Postsynaptic density protein-95 (PSD95) plays important roles in the formation, differentiation, remodeling, and maturation of neuronal synapses. This study is to estimate the potential role of PSD95 in cognitive dysfunction and synaptic injury following intracerebral hemorrhage (ICH). The interaction between PSD95 and NMDA receptor subunit NR2B-neurotransmitter nitric oxide synthase (nNOS) could form a signal protein complex mediating excitatory signaling. Besides NR2B-nNOS, PSD95 also can bind to neurexin-1-neuroligin-1 to form a complex and participates in maintaining synaptic function. In this study, we found that there were an increase in the formation of PSD95-NR2B-nNOS complex and a decrease in the formation of neurexin-1-neuroligin-1-PSD95 complex after ICH, and this was accompanied by increased neuronal death and degeneration, and behavior dysfunction. PSD95 inhibitor Tat-NR2B9c effectively inhibited the interaction between PSD95 and NR2B-nNOS, and promoted the formation of neurexin-1-nueuroligin-1-PSD95 complex. In addition, Tat-NR2B9c treatment significantly reduced neuronal death and degeneration and matrix metalloproteinase 9 activity, alleviated inflammatory response and neurobehavioral disorders, and improved the cognitive and learning ability of ICH rats. Inhibition of the formation of PSD95-NR2B-nNOS complex can rescue secondary brain injury and behavioral cognitive impairment after ICH. PSD95 is expected to be a target for improving the prognosis of patients with ICH. Title: Multifunctional 5,6-dimethoxybenzo[d]isothiazol-3(2H)-one-N-alkylbenzylamine derivatives with acetylcholinesterase, monoamine oxidases and beta-amyloid aggregation inhibitory activities as potential agents against Alzheimer's disease Xu R, Xiao G, Li Y, Liu H, Song Q, Zhang X, Yang Z, Zheng Y, Tan Z, Deng Y Ref: Bioorganic & Medicinal Chemistry, 26:1885, 2018 : PubMed ESTHER: Xu_2018_Bioorg.Med.Chem_26_1885 PubMedSearch: Xu 2018 Bioorg.Med.Chem 26 1885 PubMedID: 29500132 Abstract A series of 5,6-dimethoxybenzo[d]isothiazol-3(2H)-one-N-alkylbenzylamine derivatives were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease (AD). The in vitro assays indicated that most of these derivatives were selective AChE inhibitors with good multifunctional properties. Among them, compounds 11b and 11d displayed comprehensive advantages, with good AChE (IC50=0.29+/-0.01muM and 0.46+/-0.02muM, respectively), MAO-A (IC50=8.2+/-0.08muM and 7.9+/-0.07muM, respectively) and MAO-B (IC50=20.1+/-0.16muM and 43.8+/-2.0% at 10muM, respectively) inhibitory activities, moderate self-induced Abeta1-42 aggregation inhibitory potency (35.4+/-0.42% and 48.0+/-1.53% at 25muM, respectively) and potential antioxidant activity. In addition, the two representative compounds displayed high BBB permeability in vitro. Taken together, these multifunctional properties make 11b and 11d as a promising candidate for the development of efficient drugs against AD. Title: Butyrylcholinesterase Levels on Admission Predict Severity and 12-Month Mortality in Hospitalized AIDS Patients Xu L, Zhu B, Huang Y, Yang Z, Sun J, Xu Y, Zheng J, Kinloch S, Yin MT and Wu N <1 more author(s)> Xu L, Zhu B, Huang Y, Yang Z, Sun J, Xu Y, Zheng J, Kinloch S, Yin MT, Weng H, Wu N (- 1) Ref: Mediators Inflamm, 2018:5201652, 2018 : PubMed ESTHER: Xu_2018_Mediators.Inflamm_2018_5201652 PubMedSearch: Xu 2018 Mediators.Inflamm 2018 5201652 PubMedID: 29736152 Abstract Background: Butyrylcholinesterase (BChE) is synthesized mainly in the liver and an important marker in many infectious/inflammatory diseases, but its role in acquired immunodeficiency syndrome (AIDS) patients is not clear. We wished to ascertain if BChE level is associated with the progression/prognosis of AIDS patients. Methods: BChE levels (in U/L) were measured in 505 patients; <4500 was defined as "low" and >/=4500 as "normal." Associations between BChE level and CD4 count, WHO stage, body mass index (BMI), C-reactive protein (CRP) level, and duration of hospitalization were assessed. Kaplan-Meier curves and Cox proportional hazards model were used to assess associations between low BChE levels and mortality, after adjustment for age, CD4 count, WHO stage, and laboratory parameters. Results: A total of 129 patients (25.5%) had a lower BChE level. BChE was closely associated with CD4 count, WHO stage, CRP level, and BMI (all P < 0.001). Eighty-four patients (16.6%) died in the first year of follow-up. One-year survival was 64.5 +/- 4.5% for patients with low BChE and 87.6 +/- 1.8% for those with normal BChE (log-rank, P < 0.001). After adjustment for sex, age, BMI, WHO stage, and CD4 count, as well as serum levels of hemoglobin, sodium, and albumin, the hazard ratio was 1.8 (95% confidence interval, 1.0-3.2) for patients with a low BChE compared with those with a normal BChE (P = 0.035). Conclusion: BChE level is associated with HIV/AIDS severity and is an independent risk factor for increased mortality in AIDS patients. Title: Preventive Effect of Lactobacillus fermentum CQPC03 on Activated Carbon-Induced Constipation in ICR Mice Zhang J, Chen B, Liu B, Zhou X, Mu J, Wang Q, Zhao X, Yang Z Ref: Medicina (Kaunas), 54:, 2018 : PubMed ESTHER: Zhang_2018_Medicina.(Kaunas)_54_ PubMedSearch: Zhang 2018 Medicina.(Kaunas) 54 PubMedID: 30463207 Abstract Background and objectives: Paocai (pickled cabbage), which is fermented by lactic acid bacteria, is a traditional Chinese food. The microorganisms of Paocai were isolated and identified, and the constipation inhibition effect of one of the isolated Lactobacillus was investigated. Materials and Methods: The 16S rDNA technology was used for microbial identification. A mouse constipation model was established using activated carbon. After intragastric administration of Lactobacillus (10(8) CFU/mL), the mice were dissected to prepare pathological sections of the small intestine. Serum indicators were detected using kits, and the expression of small intestine-related mRNAs was detected by qPCR assay. Results: One strain of Lactobacillus was identified and named Lactobacillus fermentum CQPC03 (LF-CQPC03). Body weight and activated carbon propulsion rate were all higher in mice intragastrically administered with LF-CQPC03 compared with the control group, while the time to the first black stool in treated mice was lower than that in the control group. Serum assays showed that gastrin (Gas), endothelin (ET), and acetylcholinesterase (AchE) levels were significantly higher in the LF-CQPC03-treated mice than in the control group, while somatostatin (SS) levels were significantly lower than in the control mice. Mouse small intestine tissue showed that c-Kit, stem cell factor (SCF), and glial cell-derived neurotrophic factor (GDNF) mRNA expression levels were significantly higher in the LF-CQPC03 treated mice than in control mice, while transient receptor potential cation channel subfamily V member 1 (TRPV1) and inducible nitric oxide synthase (iNOS) expression levels were significantly lower in the LF-CQPC03 treated mice than in control mice. Conclusions: There is a better effect with high-dose LF-CQPC03, compared to the lower dose (LF-CQPC03-L), showing good probiotic potential, as well as development and application value. Title: Transcriptional responses in the hepatopancreas of Eriocheir sinensis exposed to deltamethrin Yang Z, Zhang Y, Jiang Y, Zhu F, Zeng L, Wang Y, Lei X, Yao Y, Hou Y and Hu K <3 more author(s)> Yang Z, Zhang Y, Jiang Y, Zhu F, Zeng L, Wang Y, Lei X, Yao Y, Hou Y, Xu L, Xiong C, Yang X, Hu K (- 3) Ref: PLoS ONE, 12:e0184581, 2017 : PubMed ESTHER: Yang_2017_PLoS.One_12_e0184581 PubMedSearch: Yang 2017 PLoS.One 12 e0184581 PubMedID: 28910412 Abstract Deltamethrin is an important pesticide widely used against ectoparasites. Deltamethrin contamination has resulted in a threat to the healthy breeding of the Chinese mitten crab, Eriocheir sinensis. In this study, we investigated transcriptional responses in the hepatopancreas of E. sinensis exposed to deltamethrin. We obtained 99,087,448, 89,086,478, and 100,117,958 raw sequence reads from control 1, control 2, and control 3 groups, and 92,094,972, 92,883,894, and 92,500,828 raw sequence reads from test 1, test 2, and test 3 groups, respectively. After filtering and quality checking of the raw sequence reads, our analysis yielded 79,228,354, 72,336,470, 81,859,826, 77,649,400, 77,194,276, and 75,697,016 clean reads with a mean length of 150 bp from the control and test groups. After deltamethrin treatment, a total of 160 and 167 genes were significantly upregulated and downregulated, respectively. Gene ontology terms "biological process," "cellular component," and "molecular function" were enriched with respect to cell killing, cellular process, other organism part, cell part, binding, and catalytic. Pathway analysis using the Kyoto Encyclopedia of Genes and Genomes showed that the metabolic pathways were significantly enriched. We found that the CYP450 enzyme system, carboxylesterase, glutathione-S-transferase, and material (including carbohydrate, lipid, protein, and other substances) metabolism played important roles in the metabolism of deltamethrin in the hepatopancreas of E. sinensis. This study revealed differentially expressed genes related to insecticide metabolism and detoxification in E. sinensis for the first time and will help in understanding the toxicity and molecular metabolic mechanisms of deltamethrin in E. sinensis. Title: Degradation of methomyl by the combination of Aminobacter sp. MDW-2 and Afipia sp. MDW-3 Zhang C, Yang Z, Jin W, Wang X, Zhang Y, Zhu S, Yu X, Hu G, Hong Q Ref: Lett Appl Microbiol, 64:289, 2017 : PubMed ESTHER: Zhang_2017_Lett.Appl.Microbiol_64_289 PubMedSearch: Zhang 2017 Lett.Appl.Microbiol 64 289 PubMedID: 28083911 Abstract Methomyl (S-methyl N-(methylcarbamoyloxy) thioacetimidate) is a kind of oxime carbamate insecticide. It is considered to be extremely toxic to nontarget organism. To date, no pure culture or consortium has been reported to have the ability to degrade methomyl completely. In this study, a methomyl-degrading enrichment E1 was obtained by using the sludge from the wastewater-treating system of a pesticide manufacturer as the original inoculant. Two bacterial strains named MDW-2 and MDW-3 were isolated from this enrichment, and they were preliminarily identified as Aminobacter sp. and Afipia sp. respectively. Strains MDW-2 and MDW-3 could coexist and degrade 50smgsl(-1) methomyl completely within 3sdays by the cooperative metabolism. Methomyl was first converted to methomyl oxime and methylcarbamic acid by strain MDW-2, and the latter could be used as the carbon source for the growth of strain MDW-2. But methomyl oxime could not be sequentially degraded by strain MDW-2. However, it could be degraded and used as the carbon source by strain MDW-3. SIGNIFICANCE AND IMPACT OF THE STUDY: This study presents a bacterial combination of Aminobacter sp. MDW-2 and Afipia sp. MDW-3, which could degrade methomyl completely by biochemical cooperation. This study also proposes the biodegradation pathway of methomyl for the first time and highlights the application potential of a bacterial combination in the remediation of methomyl-contaminated environments. Title: The Aegilops tauschii genome reveals multiple impacts of transposons Zhao G, Zou C, Li K, Wang K, Li T, Gao L, Zhang X, Wang H, Yang Z and Jia J <5 more author(s)> Zhao G, Zou C, Li K, Wang K, Li T, Gao L, Zhang X, Wang H, Yang Z, Liu X, Jiang W, Mao L, Kong X, Jiao Y, Jia J (- 5) Ref: Nat Plants, 3:946, 2017 : PubMed ESTHER: Zhao_2017_Nat.Plants_3_946 PubMedSearch: Zhao 2017 Nat.Plants 3 946 PubMedID: 29158546 Gene_locus related to this paper: horvv-m0utz9, wheat-a0a3b6c2m6, wheat-a0a3b5zwb6, wheat-a0a3b6bzs8, wheat-a0a1d5zte7 Abstract Wheat is an important global crop with an extremely large and complex genome that contains more transposable elements (TEs) than any other known crop species. Here, we generated a chromosome-scale, high-quality reference genome of Aegilops tauschii, the donor of the wheat D genome, in which 92.5% sequences have been anchored to chromosomes. Using this assembly, we accurately characterized genic loci, gene expression, pseudogenes, methylation, recombination ratios, microRNAs and especially TEs on chromosomes. In addition to the discovery of a wave of very recent gene duplications, we detected that TEs occurred in about half of the genes, and found that such genes are expressed at lower levels than those without TEs, presumably because of their elevated methylation levels. We mapped all wheat molecular markers and constructed a high-resolution integrated genetic map corresponding to genome sequences, thereby placing previously detected agronomically important genes/quantitative trait loci (QTLs) on the Ae. tauschii genome for the first time. Title: Silibinin rescues learning and memory deficits by attenuating microglia activation and preventing neuroinflammatory reactions in SAMP8 mice Jin G, Bai D, Yin S, Yang Z, Zou D, Zhang Z, Li X, Sun Y, Zhu Q Ref: Neuroscience Letters, 629:256, 2016 : PubMed ESTHER: Jin_2016_Neurosci.Lett_629_256 PubMedSearch: Jin 2016 Neurosci.Lett 629 256 PubMedID: 27276653 Abstract Silibinin was reported to be effective in reversing the learning and memory deficits of several AD animal models. These improvements are thought to be regulated by various factors, including antioxidative stress, inhibition of acetylcholinesterase activity and Abeta aggregation. However, there are still no reports that demonstrate the effect of silibinin on microglia activation in vivo. Thus, in this study, we used the senescence-accelerated mouse (SAMP8) strain to test the effects of silibinin on behavioral impairments and microglia activation-induced neuroinflammation. Silibinin treatment significantly rescued memory deficits in novel object recognition test and Morris water maze test. Silibinin treatment significantly attenuated microglial activation; down-regulated the level of the proinflammatory cytokine IL-6, anti-inflammatory cytokine IL-4, and inflammation-associated proteins, iNOS and COX-2; and further modulated MAPK to protect neural cells. These results suggest that silibinin could be a potential candidate for the therapy of neurodegenerative disorders. Title: Pharmacokinetic characterization of BMS-936561, an anti-CD70 antibody-drug conjugate, in preclinical animal species and prediction of its pharmacokinetics in humans Wang H, Rangan VS, Sung MC, Passmore D, Kempe T, Wang X, Thevanayagam L, Pan C, Rao C and Yang Z <6 more author(s)> Wang H, Rangan VS, Sung MC, Passmore D, Kempe T, Wang X, Thevanayagam L, Pan C, Rao C, Srinivasan M, Zhang Q, Gangwar S, Deshpande S, Cardarelli P, Marathe P, Yang Z (- 6) Ref: Biopharmaceutics & Drug Disposition, 37:93, 2016 : PubMed ESTHER: Wang_2016_Biopharm.Drug.Dispos_37_93 PubMedSearch: Wang 2016 Biopharm.Drug.Dispos 37 93 PubMedID: 25869904 Abstract CD70 is a tumor necrosis factor (TNF)-like type II integral membrane protein that is transiently expressed on activated T- and B-lymphocytes. Aberrant expression of CD70 was identified in both solid tumors and haematologic malignancies. BMS-936561 (alphaCD70_MED-A) is an antibody-drug conjugate composed of a fully human anti-CD70 monoclonal antibody (alphaCD70) conjugated with a duocarmycin derivative, MED-A, through a maleimide-containing citrulline-valine dipeptide linker. MED-A is a carbamate prodrug that is activated by carboxylesterase to its active form, MED-B, to exert its DNA alkylation activity. In vitro serum stability studies suggested the efficiencies of hydrolyzing the carbamate-protecting group in alphaCD70_MED-A followed a rank order of mouse > rat > > monkey > dog ~ human. Pharmacokinetics of alphaCD70_MED-A was evaluated in mice, monkeys, and dogs after single intravenous doses. In mice, alphaCD70_MED-A was cleared rapidly, with no detectable exposures after 15 min following dosing. In contrast, alphaCD70_MED-A was much more stable in monkeys and dogs. The clearance of alphaCD70_MED-A in monkeys was 58 mL/d/kg, ~2-fold faster than that in dogs (31 mL/d/kg). The human PK profiles of the total alphaCD70 and alphaCD70_MED-A were predicted using allometrically scaled monkeys PK parameters of alphaCD70 and the carbamate hydrolysis rate constant estimated in dogs. Comparing the predicted and observed human PK from the phase I study, the dose-normalized concentration-time profiles of alphaCD70_MED-A and the total alphaCD70 were largely within the 5(th) -95(th) percentile of the predicted profiles. Copyright (c) 2015 John Wiley & Sons, Ltd. Title: Enzymatic Synthesis of Glucose-Based Fatty Acid Esters in Bisolvent Systems Containing Ionic Liquids or Deep Eutectic Solvents Zhao KH, Cai YZ, Lin XS, Xiong J, Halling PJ, Yang Z Ref: Molecules, 21:, 2016 : PubMed ESTHER: Zhao_2016_Molecules_21_ PubMedSearch: Zhao 2016 Molecules 21 PubMedID: 27689970 Abstract Sugar fatty acid esters (SFAEs) are biocompatible nonionic surfactants with broad applications in food, cosmetic, and pharmaceutical industries. They can be synthesized enzymatically with many advantages over their chemical synthesis. In this study, SFAE synthesis was investigated by using two reactions: (1) transesterification of glucose with fatty acid vinyl esters and (2) esterification of methyl glucoside with fatty acids, catalyzed by Lipozyme TLIM and Novozym 435 respectively. Fourteen ionic liquids (ILs) and 14 deep eutectic solvents (DESs) were screened as solvents, and the bisolvent system composed of 1-hexyl-3-methylimidazolium trifluoromethylsulfonate ([HMIm][TfO]) and 2-methyl-2-butanol (2M2B) was the best for both reactions, yielding optimal productivities (769.6 and 397.5 micromol/h/g, respectively) which are superior to those reported in the literature. Impacts of different reaction conditions were studied for both reactions. Response surface methodology (RSM) was employed to optimize the transesterification reaction. Results also demonstrated that as co-substrate, methyl glucoside yielded higher conversions than glucose, and that conversions increased with an increase in the chain length of the fatty acid moieties. DESs were poor solvents for the above reactions presumably due to their high viscosity and high polarity. Title: Unraveling adaptation of Pontibacter korlensis to radiation and infertility in desert through complete genome and comparative transcriptomic analysis Dai J, Dai W, Qiu C, Yang Z, Zhang Y, Zhou M, Zhang L, Fang C, Gao Q and Chen X <4 more author(s)> Dai J, Dai W, Qiu C, Yang Z, Zhang Y, Zhou M, Zhang L, Fang C, Gao Q, Yang Q, Li X, Wang Z, Jia Z, Chen X (- 4) Ref: Sci Rep, 5:10929, 2015 : PubMed ESTHER: Dai_2015_Sci.Rep_5_10929 PubMedSearch: Dai 2015 Sci.Rep 5 10929 PubMedID: 26057562 Gene_locus related to this paper: 9bact-a0a0e3zf06, 9bact-a0a0e3zhq7 Abstract The desert is a harsh habitat for flora and microbial life due to its aridness and strong radiation. In this study, we constructed the first complete and deeply annotated genome of the genus Pontibacter (Pontibacter korlensis X14-1(T) = CCTCC AB 206081(T), X14-1). Reconstruction of the sugar metabolism process indicated that strain X14-1 can utilize diverse sugars, including cellulose, starch and sucrose; this result is consistent with previous experiments. Strain X14-1 is also able to resist desiccation and radiation in the desert through well-armed systems related to DNA repair, radical oxygen species (ROS) detoxification and the OstAB and TreYZ pathways for trehalose synthesis. A comparative transcriptomic analysis under gamma radiation revealed that strain X14-1 presents high-efficacy operating responses to radiation, including the robust expression of catalase and the manganese transport protein. Evaluation of 73 novel genes that are differentially expressed showed that some of these genes may contribute to the strain's adaptation to radiation and desiccation through ferric transport and preservation. Title: The organophosphate insecticide chlorpyrifos confers its genotoxic effects by inducing DNA damage and cell apoptosis Li D, Huang Q, Lu M, Zhang L, Yang Z, Zong M, Tao L Ref: Chemosphere, 135:387, 2015 : PubMed ESTHER: Li_2015_Chemosphere_135_387 PubMedSearch: Li 2015 Chemosphere 135 387 PubMedID: 26002045 Abstract The organophosphate insecticide chlorpyrifos (CPF) is known to induce neurological effects, malformation and micronucleus formation, persistent developmental disorders, and maternal toxicity in rats and mice. The binding of chlorpyrifos with DNA to produce DNA adducts leads to an increasing social concern about the genotoxic risk of CPF in human, but CPF-induced cytotoxicity through DNA damage and cell apoptosis is not well understood. Here, we quantified the cytotoxicity and potential genotoxicity of CPF using the alkaline comet assay, gammaH2AX foci formation, and the DNA laddering assay in order to detect DNA damage and apoptosis in human HeLa and HEK293 cells in vitro. Drosophila S2 cells were used as a positive control. The alkaline comet assay showed that sublethal concentrations of CPF induced significant concentration-dependent increases in single-strand DNA breaks in the treated cells compared with the control. The percentage of gammaH2AX-positive HeLa cells revealed that CPF also causes DNA double-strand breaks in a time-dependent manner. Moreover, DNA fragmentation analysis demonstrated that exposure to CPF induced a significant concentration- and time-dependent increase in cell apoptosis. We conclude that CPF is a strongly genotoxic agent that induces DNA damage and cell apoptosis. Title: Enzyme-Instructed Intracellular Molecular Self-Assembly to Boost Activity of Cisplatin against Drug-Resistant Ovarian Cancer Cells Li J, Kuang Y, Shi J, Zhou J, Medina JE, Zhou R, Yuan D, Yang C, Wang H and Xu B <3 more author(s)> Li J, Kuang Y, Shi J, Zhou J, Medina JE, Zhou R, Yuan D, Yang C, Wang H, Yang Z, Liu J, Dinulescu DM, Xu B (- 3) Ref: Angew Chem Int Ed Engl, 54:13307, 2015 : PubMed ESTHER: Li_2015_Angew.Chem.Int.Ed.Engl_54_13307 PubMedSearch: Li 2015 Angew.Chem.Int.Ed.Engl 54 13307 PubMedID: 26365295 Abstract Anticancer drug resistance demands innovative approaches that boost the activity of drugs against drug-resistant cancers without increasing the systemic toxicity. Here we show the use of enzyme-instructed self-assembly (EISA) to generate intracellular supramolecular assemblies that drastically boost the activity of cisplatin against drug-resistant ovarian cancer cells. We design and synthesize small peptide precursors as the substrates of carboxylesterase (CES). CES cleaves the ester bond pre-installed on the precursors to form the peptides that self-assemble in water to form nanofibers. At the optimal concentrations, the precursors themselves are innocuous to cells, but they double or triple the activity of cisplatin against the drug-resistant ovarian cancer cells. This work illustrates a simple, yet fundamental, new way to introduce non-cytotoxic components into combination therapies with cisplatin without increasing the systemic burden or side effects. Title: Macrophage CGI-58 deficiency activates ROS-inflammasome pathway to promote insulin resistance in mice Miao H, Ou J, Ma Y, Guo F, Yang Z, Wiggins M, Liu C, Song W, Han X and Yu L <8 more author(s)> Miao H, Ou J, Ma Y, Guo F, Yang Z, Wiggins M, Liu C, Song W, Han X, Wang M, Cao Q, Chung BH, Yang D, Liang H, Xue B, Shi H, Gan L, Yu L (- 8) Ref: Cell Rep, 7:223, 2014 : PubMed ESTHER: Miao_2014_Cell.Rep_7_223 PubMedSearch: Miao 2014 Cell.Rep 7 223 PubMedID: 24703845 Abstract Overnutrition activates a proinflammatory program in macrophages to induce insulin resistance (IR), but its molecular mechanisms remain incompletely understood. Here, we show that saturated fatty acid and lipopolysaccharide, two factors implicated in high-fat diet (HFD)-induced IR, suppress macrophage CGI-58 expression. Macrophage-specific CGI-58 knockout (MaKO) in mice aggravates HFD-induced glucose intolerance and IR, which is associated with augmented systemic/tissue inflammation and proinflammatory activation of adipose tissue macrophages. CGI-58-deficient macrophages exhibit mitochondrial dysfunction due to defective peroxisome proliferator-activated receptor (PPAR)gamma signaling. Consequently, they overproduce reactive oxygen species (ROS) to potentiate secretion of proinflammatory cytokines by activating NLRP3 inflammasome. Anti-ROS treatment or NLRP3 silencing prevents CGI-58-deficient macrophages from oversecreting proinflammatory cytokines and from inducing proinflammatory signaling and IR in the cocultured fat slices. Anti-ROS treatment also prevents exacerbation of inflammation and IR in HFD-fed MaKO mice. Our data thus establish CGI-58 as a suppressor of overnutrition-induced NLRP3 inflammasome activation in macrophages. Title: Molecular traces of alternative social organization in a termite genome Terrapon N, Li C, Robertson HM, Ji L, Meng X, Booth W, Chen Z, Childers CP, Glastad KM and Liebig J <32 more author(s)> Terrapon N, Li C, Robertson HM, Ji L, Meng X, Booth W, Chen Z, Childers CP, Glastad KM, Gokhale K, Gowin J, Gronenberg W, Hermansen RA, Hu H, Hunt BG, Huylmans AK, Khalil SM, Mitchell RD, Munoz-Torres MC, Mustard JA, Pan H, Reese JT, Scharf ME, Sun F, Vogel H, Xiao J, Yang W, Yang Z, Zhou J, Zhu J, Brent CS, Elsik CG, Goodisman MA, Liberles DA, Roe RM, Vargo EL, Vilcinskas A, Wang J, Bornberg-Bauer E, Korb J, Zhang G, Liebig J (- 32) Ref: Nat Commun, 5:3636, 2014 : PubMed ESTHER: Terrapon_2014_Nat.Commun_5_3636 PubMedSearch: Terrapon 2014 Nat.Commun 5 3636 PubMedID: 24845553 Gene_locus related to this paper: zoone-a0a067r283, zoone-a0a067qst6, zoone-a0a067rbc7, zoone-a0a067qz43, zoone-a0a067qn94, zoone-a0a067rbw9, zoone-a0a067qx93, zoone-a0a067rcf4, zoone-a0a067r8q8, zoone-a0a067rh81, zoone-a0a067r506, zoone-a0a067qxd4, zoone-a0a067qy86, zoone-a0a067qsw2, zoone-a0a067qfp9, zoone-a0a067ru91, zoone-a0a067rwu7, zoone-a0a067rmu8, zoone-a0a067r773, zoone-a0a067qlt8, zoone-a0a067qhm6, zoone-a0a067qjz2, zoone-a0a067qs20, zoone-a0a067rmu4, zoone-a0a067qty7, zoone-a0a067rk35, zoone-a0a067rk64, zoone-a0a067rj74, zoone-a0a067rp97, zoone-a0a067rjm1 Abstract Although eusociality evolved independently within several orders of insects, research into the molecular underpinnings of the transition towards social complexity has been confined primarily to Hymenoptera (for example, ants and bees). Here we sequence the genome and stage-specific transcriptomes of the dampwood termite Zootermopsis nevadensis (Blattodea) and compare them with similar data for eusocial Hymenoptera, to better identify commonalities and differences in achieving this significant transition. We show an expansion of genes related to male fertility, with upregulated gene expression in male reproductive individuals reflecting the profound differences in mating biology relative to the Hymenoptera. For several chemoreceptor families, we show divergent numbers of genes, which may correspond to the more claustral lifestyle of these termites. We also show similarities in the number and expression of genes related to caste determination mechanisms. Finally, patterns of DNA methylation and alternative splicing support a hypothesized epigenetic regulation of caste differentiation. Title: Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats Wang T, Zhao L, Liu M, Xie F, Ma X, Zhao P, Liu Y, Li J, Wang M and Zhang Y <1 more author(s)> Wang T, Zhao L, Liu M, Xie F, Ma X, Zhao P, Liu Y, Li J, Wang M, Yang Z, Zhang Y (- 1) Ref: Toxicol Appl Pharmacol, 280:169, 2014 : PubMed ESTHER: Wang_2014_Toxicol.Appl.Pharmacol_280_169 PubMedSearch: Wang 2014 Toxicol.Appl.Pharmacol 280 169 PubMedID: 24967689 Abstract Chronic exposure to low-levels of organophosphate (OP) compounds, such as chlorpyrifos (CPF), induces oxidative stress and could be related to neurological disorders. Hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. We explore whether intake of hydrogen-rich water (HRW) can protect Wistar rats from CPF-induced neurotoxicity. Rats were gavaged daily with 6.75mg/kg body weight (1/20 LD50) of CPF and given HRW by oral intake. Nissl staining and electron microscopy results indicated that HRW intake had protective effects on the CPF-induced damage of hippocampal neurons and neuronal mitochondria. Immunostaining results showed that the increased glial fibrillary acidic protein (GFAP) expression in astrocytes induced by CPF exposure can be ameliorated by HRW intake. Moreover, HRW intake also attenuated CPF-induced oxidative stress as evidenced by enhanced level of MDA, accompanied by an increase in GSH level and SOD and CAT activity. Acetylcholinesterase (AChE) activity tests showed significant decrease in brain AChE activity after CPF exposure, and this effect can be ameliorated by HRW intake. An in vitro study demonstrated that AChE activity was more intense in HRW than in normal water with or without chlorpyrifos-oxon (CPO), the metabolically-activated form of CPF. These observations suggest that HRW intake can protect rats from CPF-induced neurotoxicity, and the protective effects of hydrogen may be mediated by regulating the oxidant and antioxidant status of rats. Furthermore, this work defines a novel mechanism of biological activity of hydrogen by directly increasing the AChE activity. Title: Dual regulation of adipose triglyceride lipase by pigment epithelium-derived factor: A novel mechanistic insight into progressive obesity Dai Z, Qi W, Li C, Lu J, Mao Y, Yao Y, Li L, Zhang T, Hong H and Cai W <5 more author(s)> Dai Z, Qi W, Li C, Lu J, Mao Y, Yao Y, Li L, Zhang T, Hong H, Li S, Zhou T, Yang Z, Yang X, Gao G, Cai W (- 5) Ref: Mol Cell Endocrinol, 377:123, 2013 : PubMed ESTHER: Dai_2013_Mol.Cell.Endocrinol_377_123 PubMedSearch: Dai 2013 Mol.Cell.Endocrinol 377 123 PubMedID: 23850519 Abstract Both elevated plasma free fatty acids (FFA) and accumulating triglyceride in adipose tissue are observed in the process of obesity and insulin resistance. This contradictory phenomenon and its underlying mechanisms have not been thoroughly elucidated. Recent studies have demonstrated that pigment epithelium-derived factor (PEDF) contributes to elevated plasma FFA and insulin resistance in obese mice via the activation of adipose triglyceride lipase (ATGL). However, we found that PEDF downregulated adipose ATGL protein expression despite of enhancing lipolysis. Plasma PEDF and FFA were increased in associated with a progressive high-fat-diet, and those outcomes were also accompanied by fat accumulation and a reduction in adipose ATGL. Exogenous PEDF injection downregulated adipose ATGL protein expression and elevated plasma FFA, while endogenous PEDF neutralization significantly rescued the adipose ATGL reduction and also reduced plasma FFA in obese mice. PEDF reduced ATGL protein expression in a time- and dose-dependent manner in differentiated 3T3-L1 cells. Small interfering RNA-mediated PEDF knockdown and antibody-mediated PEDF blockage increased endogenous ATGL expression, and PEDF overexpression downregulated ATGL. PEDF resulted in a decreased half-life of ATGL and regulated ATGL degradation via ubiquitin-dependent proteasomal degradation pathway. PEDF stimulated lipolysis via ATGL using ATGL inhibitor bromoenol lactone, and PEDF also downregulated G0/G1 switch gene 2 (G0S2) expression, which is an endogenous inhibitor of ATGL activation. Overall, PEDF attenuated ATGL protein accumulation via proteasome-mediated degradation in adipocytes, and PEDF also promoted lipolysis by activating ATGL. Elevated PEDF may contribute to progressive obesity and insulin resistance via its dual regulation of ATGL. Title: Genome and transcriptome sequencing of the halophilic fungus Wallemia ichthyophaga: haloadaptations present and absent Zajc J, Liu Y, Dai W, Yang Z, Hu J, Gostincar C, Gunde-Cimerman N Ref: BMC Genomics, 14:617, 2013 : PubMed ESTHER: Zajc_2013_BMC.Genomics_14_617 PubMedSearch: Zajc 2013 BMC.Genomics 14 617 PubMedID: 24034603 Abstract BACKGROUND: The basidomycete Wallemia ichthyophaga from the phylogenetically distinct class Wallemiomycetes is the most halophilic fungus known to date. It requires at least 10% NaCl and thrives in saturated salt solution. To investigate the genomic basis of this exceptional phenotype, we obtained a de-novo genome sequence of the species type-strain and analysed its transcriptomic response to conditions close to the limits of its lower and upper salinity range. Title: Melamine induced spatial cognitive deficits associated with impairments of hippocampal long-term depression and cholinergic system in Wistar rats An L, Yang Z, Zhang T Ref: Neurobiol Learn Mem, 100C:18, 2012 : PubMed ESTHER: An_2012_Neurobiol.Learn.Mem_100C_18 PubMedSearch: An 2012 Neurobiol.Learn.Mem 100C 18 PubMedID: 23231966 Abstract Our previous studies reported that hippocampus was one of the target sites of melamine, by which the spatial cognition and hippocampal long-term potentiation (LTP) could be impaired. The aim of present study was to investigate whether cognitive behavior impairment induced by melamine was associated with the alteration of hippocampal long-term depression (LTD), and try to interpret the potential underlying mechanism. Wistar rats were used to establish an animal model and melamine administered at a dose of 300mg/kg/day for 4weeks. Water maze behavior and long-term depression (LTD) in hippocampal CA3-CA1 pathway were measured, followed by enzyme linked immunosorbent assay (ELISA), by which acetylcholine (ACh) level and acetylcholinesterase (AChE) activity were determined. Results showed that learning and reversal learning abilities were significantly impaired by melamine. The field excitatory postsynaptic potential (fEPSP) slopes were significantly higher in melamine group compared to that in control group. Furthermore, the function of cholinergic system was damaged associated with decreased Ach level and enhanced AChE activity in melamine-treated rats. It suggested that melamine induced abnormal inhibitory effect on synaptic plasticity of hippocampus, which partly resulted in reduced LTD and further damaged cognitive flexibility. Melamine could also induce dysfunctional cholinergic system, which was associated with the poor performance of animals in MWM (Morris water maze) tests. Title: Effect of interferon-alpha2b on the expression of various drug-metabolizing enzymes and transporters in co-cultures of freshly prepared human primary hepatocytes Chen C, Han YH, Yang Z, Rodrigues AD Ref: Xenobiotica, 41:476, 2011 : PubMed ESTHER: Chen_2011_Xenobiotica_41_476 PubMedSearch: Chen 2011 Xenobiotica 41 476 PubMedID: 21381897 Abstract The purpose of this study was to assess the impact of interferon-alpha2b (IFN-alpha2b) on the expression of various drug-metabolizing enzymes and transporters in freshly prepared co-cultures (parenchymal and non-parenchymal cells) of human primary hepatocytes. At therapeutically relevant concentrations (from 1000 to 3000 IU/mL), IFN-alpha2b up-regulated STAT1 (signal transducer and activator of transcription factor 1) mRNA expression. Conversely, three cytochrome P450s (CYP1A2, CYP2B6, CYP2E1), a UDP-glucuronosyltransferase (UGT2B7), a sulphotransferase (SULT1A1) and organic anion transporter (OAT2) were significantly down-regulated (~50%; P < 0.05). Western blot analysis of CYP1A2, UGT2B7 and OAT2 protein supported the mRNA data. Two peroxisome proliferator activator receptor alpha (PPARalpha)-controlled genes (pyruvate dehydrogenase kinase 4 and adipose differentiation-related protein), CYP3A4 and multidrug resistance-associated protein 2 were significantly up-regulated (up to 223%; P < 0.05). On the other hand, SULT2A1, carboxylesterase 2, organic anion transporting peptide (OATP1B1, OATP1B3, OATP2B1), organic cation transporter 1, P-glycoprotein and breast cancer resistance protein mRNA expression was not significantly affected. Western blot analysis of CYP3A4 supported the mRNA data also. The present results demonstrated complex interactions between IFN-alpha2b and hepatocytes and the observed down-regulation of CYP1A2, OAT2 and UGT2B7 is consistent with reports of drug interactions between IFN-alpha2b and drugs such as theophylline, clozapine and gemfibrozil. Title: Complete genome sequence of the nitrogen-fixing and rhizosphere-associated bacterium Pseudomonas stutzeri strain DSM4166 Yu H, Yuan M, Lu W, Yang J, Dai S, Li Q, Yang Z, Dong J, Sun L and Lin M <8 more author(s)> Yu H, Yuan M, Lu W, Yang J, Dai S, Li Q, Yang Z, Dong J, Sun L, Deng Z, Zhang W, Chen M, Ping S, Han Y, Zhan Y, Yan Y, Jin Q, Lin M (- 8) Ref: Journal of Bacteriology, 193:3422, 2011 : PubMed ESTHER: Yu_2011_J.Bacteriol_193_3422 PubMedSearch: Yu 2011 J.Bacteriol 193 3422 PubMedID: 21515765 Gene_locus related to this paper: pseu5-a4vfn0, pseu5-a4vj02, pseu5-a4vrl9, pseut-f8h720, pseu5-a4vkl7, pseu5-a4vgd4, pseu5-a4vr33 Abstract We present here the analysis of the whole-genome sequence of Pseudomonas stutzeri strain DSM4166, a diazotrophic isolate from the rhizosphere of a Sorghum nutans cultivar. To our knowledge, this is the second genome to be sequenced for P. stutzeri. The availability and analysis of the genome provide insight into the evolution of the nitrogen fixation property and identification of rhizosphere competence traits required in interactions with host plants. Title: Penicillium expansum lipase-catalyzed production of biodiesel in ionic liquids Zhang KP, Lai JQ, Huang ZL, Yang Z Ref: Bioresour Technol, 102:2767, 2011 : PubMed ESTHER: Zhang_2011_Bioresour.Technol_102_2767 PubMedSearch: Zhang 2011 Bioresour.Technol 102 2767 PubMedID: 21138789 Abstract Penicillium expansum lipase (PEL) was used to catalyze biodiesel production from corn oil in [BMIm][PF(6)](1) (an ionic liquid, IL) and tert-butanol. Both systems were optimized in terms of MeOH/oil molar ratio, reaction temperature, enzyme loading, solvent volume, and water content. The high conversion obtained in the IL (86%) as compared to that in tert-butanol (52%) demonstrates that the IL is a superior solvent for PEL-catalyzed biodiesel production. Poor yields were obtained in a series of hydrophilic ILs. Addition of salt hydrates affected biodiesel production predominantly through the specific ion (Hofmeister) effect. The impact of methanol on both activity and stability of PEL in the IL and in hexane was investigated, in comparison to the results obtained by two commonly used lipases, Novozym 435 and Lipozyme TLIM. The results substantiate that while different lipases show different resistance to methanol in different reaction systems, PEL is tolerant to methanol in both systems. Title: The sequence and de novo assembly of the giant panda genome Li R, Fan W, Tian G, Zhu H, He L, Cai J, Huang Q, Cai Q, Li B and Yang H <103 more author(s)> Li R, Fan W, Tian G, Zhu H, He L, Cai J, Huang Q, Cai Q, Li B, Bai Y, Zhang Z, Zhang Y, Wang W, Li J, Wei F, Li H, Jian M, Nielsen R, Li D, Gu W, Yang Z, Xuan Z, Ryder OA, Leung FC, Zhou Y, Cao J, Sun X, Fu Y, Fang X, Guo X, Wang B, Hou R, Shen F, Mu B, Ni P, Lin R, Qian W, Wang G, Yu C, Nie W, Wang J, Wu Z, Liang H, Min J, Wu Q, Cheng S, Ruan J, Wang M, Shi Z, Wen M, Liu B, Ren X, Zheng H, Dong D, Cook K, Shan G, Zhang H, Kosiol C, Xie X, Lu Z, Li Y, Steiner CC, Lam TT, Lin S, Zhang Q, Li G, Tian J, Gong T, Liu H, Zhang D, Fang L, Ye C, Zhang J, Hu W, Xu A, Ren Y, Zhang G, Bruford MW, Li Q, Ma L, Guo Y, An N, Hu Y, Zheng Y, Shi Y, Li Z, Liu Q, Chen Y, Zhao J, Qu N, Zhao S, Tian F, Wang X, Wang H, Xu L, Liu X, Vinar T, Wang Y, Lam TW, Yiu SM, Liu S, Huang Y, Yang G, Jiang Z, Qin N, Li L, Bolund L, Kristiansen K, Wong GK, Olson M, Zhang X, Li S, Yang H (- 103) Ref: Nature, 463:311, 2010 : PubMed ESTHER: Li_2010_Nature_463_311 PubMedSearch: Li 2010 Nature 463 311 PubMedID: 20010809 Gene_locus related to this paper: ailme-ABH15, ailme-ACHE, ailme-BCHE, ailme-d2gtv3, ailme-d2gty9, ailme-d2gu87, ailme-d2gu97, ailme-d2gve7, ailme-d2gwu1, ailme-d2gx08, ailme-d2gyt0, ailme-d2gz36, ailme-d2gz37, ailme-d2gz38, ailme-d2gz39, ailme-d2gz40, ailme-d2h5r9, ailme-d2h7b7, ailme-d2h9c9, ailme-d2h794, ailme-d2hau7, ailme-d2hau8, ailme-d2hcd9, ailme-d2hdi6, ailme-d2heu6, ailme-d2hga4, ailme-d2hqw5, ailme-d2hs98, ailme-d2hsx4, ailme-d2hti6, ailme-d2htv3, ailme-d2htz6, ailme-d2huc7, ailme-d2hwj8, ailme-d2hwy7, ailme-d2hxm1, ailme-d2hyc8, ailme-d2hyv2, ailme-d2hz11, ailme-d2hza3, ailme-d2hzr4, ailme-d2i1l4, ailme-d2i2g8, ailme-g1l7m3, ailme-g1lu36, ailme-g1m769, ailme-g1mc29, ailme-g1mdj8, ailme-g1mdr5, ailme-g1mfp4, ailme-g1mfx5, ailme-g1lj41, ailme-g1lm28, ailme-g1l3u1, ailme-g1l7l1, ailme-g1m5i3, ailme-g1l2f6, ailme-g1lji5, ailme-g1lqk3, ailme-g1l8s9, ailme-d2h717, ailme-d2h718, ailme-d2h719, ailme-d2h720, ailme-g1m5v0, ailme-g1m5y7, ailme-g1lkt7, ailme-g1l2a1, ailme-g1lsc8, ailme-g1lrp4, ailme-d2gv02, ailme-g1mik5, ailme-g1ljr1, ailme-g1lxw7, ailme-d2h8b5, ailme-d2h2r2, ailme-d2h9w7, ailme-g1meh3, ailme-g1m719 Abstract Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes. Title: Identification of the novel protein FAM172A, and its up-regulation by high glucose in human aortic smooth muscle cells Li L, Dong X, Leong MC, Zhou W, Yang Z, Chen F, Bao Y, Jia W, Hu R Ref: Int J Mol Med, 26:483, 2010 : PubMed ESTHER: Li_2010_Int.J.Mol.Med_26_483 PubMedSearch: Li 2010 Int.J.Mol.Med 26 483 PubMedID: 20818486 Gene_locus related to this paper: human-f172a Abstract The family with sequence similarity 172, member A (FAM172A) is a hypothetical protein. We recently cloned the FAM172A gene from normal human aortic tissues. In a previous study we also showed that the FAM172A gene was up-regulated by high glucose levels in macrophages. In the present study, we further identified the FAM172A protein at the level of translation and studied the effects of high glucose levels on its expression in human aortic smooth muscle cells. The FAM172A gene was subcloned into the eukaryotic expression vectors, PDC315 and pEGFP-N2. The cloned sequence shows an open reading frame of 1251 nucleotides encoding a protein of 416 amino acids. We further expressed the recombinant FAM172A protein and generated rabbit anti-human FAM172A polyclonal antibodies. The FAM172A protein was identified for the first time at the translation level by Western blot analysis. Western blotting also demonstrated that the FAM172A protein could be detected in human aortic endothelial, human aortic smooth muscle cells and THP-1-derived macrophages, the highest expression being observed in the human aortic smooth muscle cells. By a combination of bioinformatics and confocal laser scanning microscopy, we found that the FAM172A protein in HEK293 cells, was mainly located in the nucleus, and that there was an Arb2 conserved domain in the FAM172A protein sequence. We also presented evidence that the FAM172 protein expression in human aortic smooth muscle cells was up-regulated by high glucose levels in a concentration-dependent and time-course manner. We speculated that as a novel protein, FAM172A could be involved in the pathogenesis of high glucose-induced vascular damage. Title: Molecular cloning and characterization of an acetylcholinesterase cDNA in the brown planthopper, Nilaparvata lugens Yang Z, Chen J, Chen Y, Jiang S Ref: J Insect Sci, 10:102, 2010 : PubMed ESTHER: Yang_2010_J.Insect.Sci_10_102 PubMedSearch: Yang 2010 J.Insect.Sci 10 102 PubMedID: 20874389 Gene_locus related to this paper: nillu-ACHE2 Abstract A full cDNA encoding an acetylcholinesterase (AChE, EC 3.1.1.7) was cloned and characterized from the brown planthopper, Nilaparvata lugens Stal (Hemiptera: Delphacidae). The complete cDNA (2467 bp) contains a 1938-bp open reading frame encoding 646 amino acid residues. The amino acid sequence of the AChE deduced from the cDNA consists of 30 residues for a putative signal peptide and 616 residues for the mature protein with a predicted molecular weight of 69,418. The three residues (Ser242, Glu371, and His485) that putatively form the catalytic triad and the six Cys that form intra-subunit disulfide bonds are completely conserved, and 10 out of the 14 aromatic residues lining the active site gorge of the AChE are also conserved. Northern blot analysis of poly(A)+ RNA showed an approximately 2.6-kb transcript, and Southern blot analysis revealed there likely was just a single copy of this gene in N. lugens. The deduced protein sequence is most similar to AChE of Nephotettix cincticeps with 83% amino acid identity. Phylogenetic analysis constructed with 45 AChEs from 30 species showed that the deduced N. lugens AChE formed a cluster with the other 8 insect AChE2s. Additionally, the hypervariable region and amino acids specific to insect AChE2 also existed in the AChE of N. lugens. The results revealed that the AChE cDNA cloned in this work belongs to insect AChE2 subgroup, which is orthologous to Drosophila AChE. Comparison of the AChEs between the susceptible and resistant strains revealed a point mutation, Gly185Ser, is likely responsible for the insensitivity of the AChE to methamidopho in the resistant strain. Title: The genome of the cucumber, Cucumis sativus L Huang S, Li R, Zhang Z, Li L, Gu X, Fan W, Lucas WJ, Wang X, Xie B and Du Y <77 more author(s)> Huang S, Li R, Zhang Z, Li L, Gu X, Fan W, Lucas WJ, Wang X, Xie B, Ni P, Ren Y, Zhu H, Li J, Lin K, Jin W, Fei Z, Li G, Staub J, Kilian A, van der Vossen EA, Wu Y, Guo J, He J, Jia Z, Tian G, Lu Y, Ruan J, Qian W, Wang M, Huang Q, Li B, Xuan Z, Cao J, Asan, Wu Z, Zhang J, Cai Q, Bai Y, Zhao B, Han Y, Li Y, Li X, Wang S, Shi Q, Liu S, Cho WK, Kim JY, Xu Y, Heller-Uszynska K, Miao H, Cheng Z, Zhang S, Wu J, Yang Y, Kang H, Li M, Liang H, Ren X, Shi Z, Wen M, Jian M, Yang H, Zhang G, Yang Z, Chen R, Ma L, Liu H, Zhou Y, Zhao J, Fang X, Fang L, Liu D, Zheng H, Zhang Y, Qin N, Li Z, Yang G, Yang S, Bolund L, Kristiansen K, Li S, Zhang X, Wang J, Sun R, Zhang B, Jiang S, Du Y (- 77) Ref: Nat Genet, 41:1275, 2009 : PubMed ESTHER: Huang_2009_Nat.Genet_41_1275 PubMedSearch: Huang 2009 Nat.Genet 41 1275 PubMedID: 19881527 Gene_locus related to this paper: cucsa-a0a0a0ktw5, cucsa-a0a0a0lnt6, cucsa-a0a0a0kpn7, cucsa-a0a0a0lvt9, cucsa-a0a0a0kdx8, cucsa-a0a0a0m228, cucsa-a0a0a0kz31, cucsa-a0a0a0k5t5, cucsa-a0a0a0kfs7, cucsa-a0a0a0kjj7, cucsa-a0a0a0kzs7, cucsa-a0a0a0l0a6, cucsa-a0a0a0l4w4, cucsa-a0a0a0lpz0, cucsa-a0a0a0ls66 Abstract Cucumber is an economically important crop as well as a model system for sex determination studies and plant vascular biology. Here we report the draft genome sequence of Cucumis sativus var. sativus L., assembled using a novel combination of traditional Sanger and next-generation Illumina GA sequencing technologies to obtain 72.2-fold genome coverage. The absence of recent whole-genome duplication, along with the presence of few tandem duplications, explains the small number of genes in the cucumber. Our study establishes that five of the cucumber's seven chromosomes arose from fusions of ten ancestral chromosomes after divergence from Cucumis melo. The sequenced cucumber genome affords insight into traits such as its sex expression, disease resistance, biosynthesis of cucurbitacin and 'fresh green' odor. We also identify 686 gene clusters related to phloem function. The cucumber genome provides a valuable resource for developing elite cultivars and for studying the evolution and function of the plant vascular system. Title: Does the lipR gene of tubercle bacilli have a role in tuberculosis transmission and pathogenesis? Sheline KD, France AM, Talarico S, Foxman B, Zhang L, Marrs CF, Bates JH, Cave MD, Yang Z Ref: Tuberculosis (Edinb), 89:114, 2009 : PubMed ESTHER: Sheline_2009_Tuberculosis.(Edinb)_89_114 PubMedSearch: Sheline 2009 Tuberculosis.(Edinb) 89 114 PubMedID: 19027362 Abstract Mycobacterium tuberculosis lipases, a diverse class of enzymes involved in lipid metabolism, may have an important role in tuberculosis (TB) pathogenesis. We explored the association of large sequence polymorphism (LSP) in one of the M. tuberculosis lipase-encoding genes, lipR (Rv3084), with patient characteristics using a population-based sample of clinical isolates to elucidate the potential role of lipR in TB pathogenesis. LSP in lipR was found in 104 (15.6%) of 665 isolates, of which 96% belonged to principal genetic group 3. When linkage by molecular type and epidemiologic evidence were compared, molecularly clustered cases infected with a lipR LSP isolate were more often epidemiologically linked than clustered cases infected with a lipR wild-type isolate. Further epidemiologic and functional studies are necessary to determine if the association between this lipR LSP and recent transmission we identified in this population reflects a functional role of lipR in TB transmission and pathogenesis or other unidentified mechanisms. Title: [Case-controlled study of entecavir treatment for chronic severe hepatitis B] Xiao GM, He KY, Jia WD, Lei CL, Yang Z Ref: Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi, 23:56, 2009 : PubMed ESTHER: Xiao_2009_Zhonghua.Shi.Yan.He.Lin.Chuang.Bing.Du.Xue.Za.Zhi_23_56 PubMedSearch: Xiao 2009 Zhonghua.Shi.Yan.He.Lin.Chuang.Bing.Du.Xue.Za.Zhi 23 56 PubMedID: 19799020 Abstract OBJECTIVE: To evaluate the efficacy and safety of entecavir (ETV) treatment for chronic severe hepatitis B. METHODS: 78 patients with chronic severe hepatitis B and positive HBV DNA were divided into ETV group and control group, each group had 39 patients. ETV group was given the same conventional therapy as control group, and was treated with ETV. The change of liver function, PTA, HBV DNA level were observed, and adverse events were recorded. The effective rate of treatment between ETV group and control group, the baseline characteristics between the effective cases and non-responsive cases after ETV treatment were compared at week 12. RESULTS: The baseline characteristics were well balanced between ETV group and control group. The effective rate of ETV group was 56.41% versus 33.33% of control group at week 12 (P = 0.0405). The effective rate of ETV group was higher than that of control group, in the early stage of chronic severe hepatitis B (P = 0.0275), but there was no statistically significant in the middle or late stage (P = 0.4687). The comparison result of baseline characteristics between the effective and non-responsive cases after ETV treatment showed: there were statistically different in age, bilirubin level, HBV DNA level and stage of the severe hepatitis, proportion of cirrhosis, but no statistically different in cholinesterase level, alpha-fetoprotein level and sex ratio, the proportion of ascites, positive HBeAg (P > 0.05). No serious adverse events occurred. CONCLUSIONS: ETV improves the curative effect when used in the early stage of chronic severe hepatitis B, and may not in the middle and late stage. The curative effect of ETV may be affected by age, bilirubin level, HBV DNA level and stage of the severe hepatitis, cirrhosis. ETV has good security in the treatment for chronic severe hepatitis B. Title: Modified TLC bioautographic method for screening acetylcholinesterase inhibitors from plant extracts Yang Z, Zhang X, Duan D, Song Z, Yang M, Li S Ref: J Sep Sci, 32:3257, 2009 : PubMed ESTHER: Yang_2009_J.Sep.Sci_32_3257 PubMedSearch: Yang 2009 J.Sep.Sci 32 3257 PubMedID: 19697313 Abstract The present work describes modifications to an existing TLC bioautographic method for detecting acetylcholinesterase inhibitors from plant extracts. The basic principle of the method is that the enzyme converts 1-naphthyl acetate into naphthol which reacts with Fast Blue B salt to make a purple-colored background on the TLC plates. Inhibitors of acetylcholinesterases produced white spots on the background. Our modifications involve changes in the concentration of the enzyme, the reagents, and the time of the reaction. With these changes, the consumption of the enzyme was reduced by 85% and the detection limits were decreased remarkably. Title: alpha-Actinin interacts with rapsyn in agrin-stimulated AChR clustering Dobbins GC, Luo S, Yang Z, Xiong WC, Mei L Ref: Mol Brain, 1:18, 2008 : PubMed ESTHER: Dobbins_2008_Mol.Brain_1_18 PubMedSearch: Dobbins 2008 Mol.Brain 1 18 PubMedID: 19055765 Abstract AChR is concentrated at the postjunctional membrane at the neuromuscular junction. However, the underlying mechanism is unclear. We show that alpha-actinin, a protein known to cross-link F-actin, interacts with rapsyn, a scaffold protein essential for neuromuscular junction formation. alpha-Actinin, rapsyn, and surface AChR form a ternary complex. Moreover, the rapsyn-alpha-actinin interaction is increased by agrin, a factor known to stimulate AChR clustering. Downregulation of alpha-actinin expression inhibits agrin-mediated AChR clustering. Furthermore, the rapsyn-alpha-actinin interaction can be disrupted by inhibiting Abl and by cholinergic stimulation. Together these results indicate a role for alpha-actinin in AChR clustering. Title: Molecular dynamics of detoxification and toxin-tolerance genes in brown planthopper (Nilaparvata lugens Stal., Homoptera: Delphacidae) feeding on resistant rice plants Yang Z, Zhang F, He Q, He G Ref: Archives of Insect Biochemistry & Physiology, 59:59, 2005 : PubMed ESTHER: Yang_2005_Arch.Insect.Biochem.Physiol_59_59 PubMedSearch: Yang 2005 Arch.Insect.Biochem.Physiol 59 59 PubMedID: 15898115 Abstract To investigate the molecular response of brown planthopper, Nilaparvata lugens (BPH) to BPH-resistant rice plants, we isolated cDNA fragments of the genes encoding for carboxylesterase (CAR), trypsin (TRY), cytochrome P450 monooxygenase (P450), NADH-quinone oxidoreductase (NQO), acetylcholinesterase (ACE), and Glutathione S-transferase (GST). Expression profiles of the genes were monitored on fourth instar nymphs feeding on rice varieties with different resistance levels. Northern blot hybridization showed that, compared with BPH reared on susceptible rice TN1, expression of the genes for P450 and CAR was apparently up-regulated and TRY mRNA decreased in BPH feeding on a highly resistant rice line B5 and a moderately resistant rice variety MH63, respectively. Two transcripts of GST increased in BPH feeding on B5; but in BPH feeding on MH63, this gene was inducible and its expression reached a maximum level at 24 h, and then decreased slightly. The expression of NQO gene was enhanced in BPH on B5 plants but showed a constant expression in BPH on MH63 plants. No difference in ACE gene expression among BPH on different rice plants was detected by the RT-PCR method. The results suggest these genes may play important roles in the defense response of BPH to resistant rice. Title: [Simultaneous determination of organophosphorus and pyrethroid pesticide residues in vegetables by GC] Hong W, Chen Z, Yang Z Ref: Se Pu, 22:289, 2004 : PubMed Title: Variability in human sensitivity to 1,3-butadiene: Influence of the allelic variants of the microsomal epoxide hydrolase gene Abdel-Rahman SZ, El-Zein RA, Ammenheuser MM, Yang Z, Stock TH, Morandi M, Ward JB, Jr. Ref: Environmental & Molecular Mutagenesis, 41:140, 2003 : PubMed ESTHER: Abdel-Rahman_2003_Environ.Mol.Mutagen_41_140 PubMedSearch: Abdel-Rahman 2003 Environ.Mol.Mutagen 41 140 PubMedID: 12605384 Abstract The carcinogenic effects of 1,3-butadiene (BD), a chemical widely used in the rubber industry, are thought to be due to its epoxide metabolites. In humans, these epoxides are detoxified predominantly by hydrolysis, a reaction mediated by the microsomal epoxide hydrolase (mEH) enzyme. The mEH gene is polymorphic and the most common mEH coding-region variants detected in human populations are the two amino acid polymorphisms Tyr113His and His139Arg. Polymorphic amino acid substitutions at residues 113 and 139 in the human mEH protein can associate in four distinct combinations: Tyr113/His139, Tyr113/Arg139, His113/His139, and His113/Arg139. In vitro studies have shown that each of these genotypes has a unique mEH protein level that can affect net mEH enzymatic activity. In the current study, we examined the relationships among the genotypes involving these two polymorphisms and the mutagenic responses associated with occupational exposure to BD. We studied 49 nonsmoking workers from two styrene-butadiene rubber facilities in southeast Texas using the autoradiographic HPRT mutant lymphocyte assay as a biomarker of genotoxic effect. We genotyped the study participants simultaneously for both polymorphisms, using a multiplex PCR assay developed in our laboratory, and the subjects were assigned to a specific group based on the predicted mEH activity associated with their genotypes (low, intermediate, and high). In the study population, 67% were exposed to low BD levels of <150 ppb (measured by personal badge dosimeters) and 33% were exposed to >150 ppb (mean 2,244 ppb). In the BD low-exposure group, the mEH genotypes had no significant effect on the HPRT variant (mutant) frequency (Vf). In the high-exposure group (BD > 150 ppb), individuals with genotypes associated with low mEH activity had a significant (P < 0.05) 3-fold increase in HPRT Vf (Vf +/- SEM = 13.95 +/- 2.15 x 10(-6)) compared to high-activity individuals (4.41 +/- 1.19 x 10(-6)), and a 2-fold increase in Vf compared to intermediate-activity individuals (6.44 +/- 2.09 x 10(-6)). Our results indicate that mEH genotypes may play a significant role in human sensitivity to the genotoxic effects of exposure to BD. | |||||||
|
